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Objectives: This study examined the association between life-space activities and incident dementia among older adults., Study Design: A prospective study., Setting and Participants: This study included 2740 older adults (mean age 74.4 years; SD ± 6.2 years; range 65-99 years; 58.8% women)., Methods: Life-space activities were assessed using the Active Mobility Index (AMI). Incident dementia was determined using medical insurance data and long-term care insurance data (mean follow-up, 53.7 months)., Results: During the follow-up period, 326 participants (11.9%) had incident dementia. Participants were classified into 3 groups based on AMI score tertiles: tertile 1, ≤52; tertile 2, 53-77; and tertile 3, ≥78. The Cox proportional hazards model was used to examine the association between AMI scores and incident dementia. Individuals with higher scores had lower hazard ratios (HRs) (tertile 1: reference; tertile 2: HR, 0.67; 95% confidence interval [CI], 0.52-0.87; P = .002; tertile 3: HR, 0.38; 95% CI, 0.27-0.53; P < .001; P for trend: <.001). Both the physical and social AMI sub-scores were associated with dementia (P for trend: <.001)., Conclusions and Implications: Restricted life-space activity, as assessed using the AMI, was associated with the risk of dementia. In addition, both the physical and social sub-scores were associated with dementia., Competing Interests: Disclosure The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages. Recently, a small case series reported the efficacy of dexamethasone palmitate (DP) in HLH. Here, we present the results of a nationwide survey in Japan detailing 14 cases of EBV-HLH treated with DP in children. One week after DP initiation, fever, cytopenia, and splenomegaly resolved in 77%, 38%, and 77% of patients (10, 5, and 10 of 13 patients, 1 missing). A 50% or greater reduction in ferritin levels was observed in 62% of patients (8 of 13 patients, 1 missing). In addition, the attending physician judged DP to be effective or partially effective in 12/14 (86%) patients. DP-related adverse events were uncommon, with only two infectious events reported. Thus, DP can be a therapeutic option for EBV-HLH., Competing Interests: Declarations. Conflict of interest: Yozo Nakazawa is an editor of International Journal of Hematology. All authors declare no competing financial interests., (© 2024. Japanese Society of Hematology.)

Purpose: To evaluate differences in the incidence of ocular complications among pediatric and young adult patients with non-infectious uveitis receiving immunosuppressive therapy (IMT), according to the time from uveitis onset to IMT initiation in Japan., Methods: Patients aged < 20 years exhibiting uveitis treated with IMT (e.g. methotrexate, cyclosporine, infliximab, or adalimumab) were categorized into three groups according to the time from uveitis onset to IMT initiation: ≤6 months, early IMT group; 7 months to 2 years, intermediate IMT group; and ≥ 2 years, late IMT group. The percentage of ocular complications was compared among these groups. Laser flare values were recorded to evaluate disruption of the blood-aqueous barrier (BAB)., Results: Forty-three patients (84 eyes) who received IMT during the follow-up period were included. Among them, 28 patients (65.1%) experienced ≥ 1 ocular complication, with percentage of 56.0% in the early IMT group, 77.8% in the intermediate group, and 77.8% in the late group. Common complications were cataract (27.4%), posterior synechiae (17.9%), and macular edema (10.7%). The early IMT group did not require surgical intervention. The late IMT group experienced a high percentage of ocular complications despite IMT initiation. The mean laser flare value during follow-up was consistently higher in the late group (113.2 pc/ms) than in the early group (14.4 pc/ms) and intermediate group (28.7 pc/ms)., Conclusion: In pediatric and young adult patients with chronic non-infectious uveitis, early IMT initiation may prevent permanent breakdown of the BAB, reduce the incidence of ocular complications, and decrease the need for surgical intervention.

Aim: Nearly half of older adults with frailty experience chronic pain. Chronic pain contributes to activity restrictions. Decreased physical activity with chronic pain is associated not only with physical dysfunction but also with reduced engagement in social activities. We aimed to verify the hypothesis that chronic pain and decreased physical activity are associated with social frailty incidence., Methods: The study included 1198 community-dwelling older adults (aged 70.2 ± 6.3 years) without social frailty at baseline. Chronic pain, physical activity and basic information were assessed at baseline. The participants were divided into two groups based on the presence (yes, n = 167) or absence (no, n = 1031) of chronic low back pain. The incidence of social frailty was investigated during the follow-up examination after 2.5 years., Results: Binomial logistic regression analysis showed that older adults with chronic low back pain and low step counts had a higher odds ratio for the development of incident social frailty than older adults without chronic low back pain and high step counts (odds ratio 1.89, 95% confidence interval 1.03-3.46)., Conclusion: Our results suggest that a combination of chronic low back pain and low step counts is associated with the incidence of social frailty. Further research is required to establish intervention methods for pain and decreased physical activity to prevent social frailty. Geriatr Gerontol Int 2024; ••: ••-••., (© 2024 Japan Geriatrics Society.)

Aim: Driving cessation is strongly associated with adverse health outcomes in older adults. Although numerous studies have focused on driving skill interventions for safe driving, the effects of interventions on car accidents remain unclear. We designed a randomized controlled trial to examine the effects of driving skill training on the prevention of car accidents among community-dwelling older adults using on-road training., Methods: A total of 1408 community-dwelling older drivers aged ≥65 years participated in the randomized controlled trial with blinded endpoint assessment. Participants randomized to the intervention group (n = 697) underwent four sessions, with 200 min re-training focused on the problem of driving in the older people. Controls (n = 697) received one classroom education session. On-road driving performance was assessed by certified driving school instructors in a driving school. The primary endpoint is an incident car accident, which will be detected based on the Japanese national car accident report data, after 24 months., Discussion: This study has the potential to provide the first evidence of the effectiveness of on-road driving skill training regarding the prevention of car accidents. If our trial results show a lower number of car accidents due to driving skill training, this kind of intervention will provide an effective method for maintaining safe driving. These results will be disseminated to the appropriate national transportation agencies to improve or modify safe driving policies and possibly extend the validity of driver's licenses for older adults., Trial Registration: UMIN-CTR (identification number: UMIN000034709). Registered 31 October 2018. Geriatr Gerontol Int 2024; 24: 1218-1222., (© 2024 Japan Geriatrics Society.)

Introduction: Understanding the heterogeneity of brain structure in individuals with the Motoric Cognitive Risk Syndrome (MCR) may improve the current risk assessments of dementia., Methods: We used data from 6 cohorts from the MCR consortium (N=1987). A weakly-supervised clustering algorithm called HYDRA was applied to volumetric MRI measures to identify distinct subgroups in the population with gait speeds lower than one standard deviation (1SD) above mean., Results: Three subgroups (Groups A, B & C) were identified through MRI-based clustering with significant differences in regional brain volumes, gait speeds, and performance on Trail Making (Part-B) and Free and Cued Selective Reminding Tests., Discussion: Based on structural MRI, our results reflect heterogeneity in the population with moderate and slow gait, including those with MCR. Such a data-driven approach could help pave new pathways toward dementia at-risk stratification and have implications for precision health for patients., Competing Interests: HMB serves as a consultant for Neural+. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He also receives support from the Migraine Research Foundation and the National Headache Foundation and research grants from TEVA, Satsuma and Amgen. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock and stock options in Axon, Biohaven Holdings, CoolTech and Manistee; serves as consultant, advisory board member, or has received honoraria from: Abbvie (Allergan), American Academy of Neurology, American Headache Society, Amgen, Avanir, Axon, Axsome, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s (Promius), Electrocore, Eli Lilly, eNeura Therapeutics, Equinox, GlaxoSmithKline, Grifols, Lundbeck (Alder), Manistee, Merck, Pernix, Pfizer, Satsuma, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. JV serves as an Advisory Committee Member for MedRhythms, and a holds a uncompensated voluntary position at CatchU. Authors BTN, AE, KKP, EA, VGPK, SV, RB, OB, TD, HS, SM, and SA do not have any conflicts of interest to disclose.

Objectives: This study aimed to investigate the association between falls and social frailty and its components among older Japanese adults., Methods: This is a cross-sectional study. Participants were categorized into 3 groups based on the number of falls in the past year: no fall (none), a single fall (occasional), and more than one fall (recurrent). The participants who met 2 or more of the following criteria were defined as socially frail: living alone, going out less frequently compared with the previous year, rarely visiting friends, feeling unhelpful to friends or family, and not talking with someone daily., Results: A total of 4,495 older Japanese adults living in a community analyzed in this study (51.0% women). Of the participants in this study, 3,851 (85.7%) were categorized as none, 443 (9.9%) as occasional, and 201 (4.5%) as recurrent. The proportion of participants considered socially frail was 11.5% in this study. Recurrent falls were associated with social frailty, even after adjusting for covariates (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.01-2.19). The experience of recurrent falls was associated with the following components: "feeling unhelpful to friends and family" (OR: 1.62; 95% CI: 1.14-2.31) and "going outside less frequently compared with last year" (OR: 1.57; 95% CI: 1.06-2.31)., Discussion: Among older Japanese adults, recurrent falls were associated with social frailty and with 2 of its components in particular: social roles and social participation. Future longitudinal studies should be conducted to gain insight into any causal relationships between these variables., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series., Methods and Analysis: This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over., Ethics and Dissemination: This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians., Trial Registration Number: jRCTs041210027., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A previous study suggested older drivers with subjective memory concerns (SMC) had increased odds of experiencing car collisions, but whether SMC in different contexts and the number of SMC applicable items change this association is unknown. The aim of this study was to examine the association between SMC and car collisions among older drivers in Japan., Methods: This cross-sectional study was conducted using data from a Japanese community-based cohort study. Participants were community-dwelling older adults aged ≥60 years. SMC was assessed using five questions: 1) "Do you feel you have more problems with memory than most?" 2) "Do you have any difficulty with your memory?" 3) "Do you forget where you have left things more than you used to?" 4) "Do you forget the names of close friends or relatives?" and 5) "Do other people find you forgetful?" Participants were asked about their experiences with car collisions during the previous two years., Results: A total of 13,137 older drivers (72.1 ± 5.5 years old, and 43.6 % female) were analyzed. Cochran-Armitage trend test showed that as the number of SMC applicable items increased, the percentage of the experiences of car collisions significantly increased (6.8 %-15.8 %, P < 0.001). Logistic regression models showed each SMC question was associated with an increased odds ratio (OR) of car collisions (OR 1.26 to 1.71, all P < 0.001) after adjusting for confounding factors. As the number of SMC applicable items increased, the OR of car collisions significantly increased (OR 1.19 to 2.28, all P < 0.05, P for trend <0.001)., Conclusions: This cross-sectional study among community-dwelling older drivers in Japan suggested each SMC question and the number of applicable items were associated with car collisions. SMC may be a sign of increased risk of traffic incidents for older drivers., Competing Interests: None., (© 2024 The Authors.)

Introduction: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI)., Methods: Participants aged 65-85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months., Results: Of 531 participants, 406 completed the trial. The between-group difference in composite score changes was 0.047 (95% CI: -0.029 to 0.124). Secondary analyses indicated positive impacts of interventions on several secondary health outcomes. The interventions appeared to be particularly effective for individuals with high attendance during exercise sessions and those with the apolipoprotein E ε4 allele and elevated plasma glial fibrillary acidic protein levels., Discussion: The multidomain intervention showed no efficacy in preventing cognitive decline. Further research on more efficient strategies and suitable target populations is required., Highlights: This trial evaluated the efficacy of multidomain intervention in individuals with MCI. The trial did not show a significant difference in preplanned cognitive outcomes. Interventions had positive effects on a wide range of secondary health outcomes. Those with adequate adherence or high risk of dementia benefited from interventions., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: This study aimed to examine the impact of negative and positive life events on the development of social frailty., Design: Population-based longitudinal study., Setting and Participants: This study was set in the Japanese community cohort and included 2174 adults aged ≥65 years without social frailty at baseline., Methods: We assessed the experiences of 6 negative and positive life events (increase in economic difficulties, illness or injury of spouse, death of family or friends, marriage of children or grandchildren, birth of grandchildren or great-grandchildren, and making new friends) in the 15 months after baseline. We followed the social frailty status of the participants and identified the development of social frailty 48 months after the baseline. Social frailty was operationally defined as having 2 or more of Makizako's 5 items (going out less frequently, rarely visiting friends, not feeling helpful to friends or family, living alone, and not talking to someone daily)., Results: Among 2174 participants without social frailty at baseline, 161 (7.4%) developed social frailty after 48 months. Multivariate logistic regression models on each life event and development of social frailty showed that illness or injury of spouse was significantly associated with a higher risk of subsequent social frailty [adjusted odds ratio (OR), 1.74; 95% CI, 1.10-2.74] and making new friends was significantly associated with lower risk of subsequent social frailty (adjusted OR, 0.38; 95% CI, 0.27-0.54). No significant ORs of social frailty were found for other life events., Conclusions and Implications: Life events in later life have both positive and negative impacts on the development of social frailty, depending on the nature of the event. To prevent social frailty, it may be important to monitor negative life events and promote positive life events in later life., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: The combined effect of physical frailty and social isolation on the need to make use of long-term care insurance (LTCI) among older adults remains unknown. Thus this study investigates the association between physical frailty, social isolation, and the use of LTCI among older adults in Japan., Study Design: This is a prospective observational study., Main Outcome Measures: Physical frailty is defined as limitations in strength, mobility, and physical activity, as well as exhaustion and weight loss. People with one or two indicators were categorized as pre-frail. Participants with a score of 1 point or more on the social isolation scale were defined as being socially isolated. Participants were followed up monthly for two years to check whether incident certification of care had been required., Results: Data on 4576 community-dwelling independent older adults (mean age, 73.9 ± 5.5 years, 2032 men, 2544 women) were analyzed. A time-dependent Cox proportional hazards regression model showed that individuals with pre-frailty without social isolation (hazard ratio [HR] 2.02, 95 % confidence interval [CI] 1.40-2.91), pre-frailty with social isolation (HR 2.36, 95 % CI 1.62-3.43), frailty without social isolation (HR 2.98, 95 % CI 1.83-4.85), and frailty with social isolation (HR 3.19, 95 % CI 2.07-4.91) had significantly higher risks of needing to make use of LTCI than those with no frailty and without social isolation. This higher risk was non-significant among individuals with no frailty and social isolation (HR 1.28, 95 % CI 0.78-2.10)., Conclusion: Combined frailty and social isolation among older adults should be addressed to prevent adverse health outcomes, including use of LTCI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: CHARGE syndrome is a congenital malformation syndrome caused by heterozygous mutations in the CHD7 gene. Severe combined immunodeficiency (SCID) arises from congenital athymia called CHARGE/complete DiGeorge syndrome. While cultured thymus tissue implantation (CTTI) provides an immunological cure, hematopoietic cell transplantation (HCT) is an alternative option for immuno-reconstitution of affected infants. We aimed to clarify the clinical outcomes of patients with athymic CHARGE syndrome after HCT., Methods: We studied the immunological reconstitution and outcomes of four patients who received non-conditioned unrelated donor cord blood transplantation (CBT) at Kyushu University Hospital from 2007 to 2022. The posttransplant outcomes were compared with the outcomes of eight reported patients., Results: Four index cases received CBT 70-144 days after birth and had no higher than grade II acute graft-versus-host disease. One infant was the first newborn-screened athymic case in Japan. They achieved more than 500/μL naïve T cells with balanced repertoire 1 month post transplant, and survived more than 12 months with home care. Twelve patients including the index cases received HCT at a median 106 days after birth (range: 70-195 days). One-year overall survival rate was significantly higher in patients who underwent non-conditioned HCT than in those who received conditioned HCT (100% vs. 37.5%, p = .02). Nine patients died, and the major cause of death was cardiopulmonary failure., Conclusions: Athymic infants achieved a prompt reconstitution of non-skewing naïve T cells after non-conditioned CBT that led to home care in infancy without significant infections. Non-conditioned CBT is a useful bridging therapy for newborn-screened cases toward an immunological cure by CTTI., (© 2023 Wiley Periodicals LLC.)

About 100 cases of Langerhans cell histiocytosis (LCH) occur annually in Japan. It predominantly occurs in infants, presenting as multisystem disease or multifocal bone involvement. However, LCH can also occur in adults aged 20 to 40. Single-system skin involvement is rare, with most cases presenting with multisystem disease, including bone lesions, which respond to chemotherapy. In adults, lung lesions that improve with smoking cessation are well-known, although multisystem disease is more common and requires aggressive therapeutic intervention similar to that in children. In some infant cases, progression of liver, spleen, and bone marrow lesions can be difficult to control and can become severe. However, targeted molecular therapies are now available as a lifesaving option. More than 30% of cases of multisystem LCH recur at least once, often leading to long-term complications. In particular, the emergence of central diabetes insipidus, anterior pituitary dysfunction, and central nervous system neurodegenerative disorders several years after the diagnosis of LCH is a unique feature not observed in other diseases. New therapeutic strategies are needed to counter these problems.

Background: Social networks and social participation have protective effects on cognitive function maintenance and Alzheimer's disease and general dementia development., Objective: We aimed to investigate the association between conversations and dementia incidence in older adults., Methods: This longitudinal prospective cohort study used population data from the National Center for Geriatric and Gerontology-Study of Geriatric Syndromes (NCGG-SGS) from September 2015 to February 2017. The database included 4,167 individuals in Japan aged ≥60 years who were generally healthy and without major cognitive impairment. Participants were classified into two groups according to six daily conversation measures at baseline. The conversation index was calculated as a composite score for these measures. Participants were tracked monthly over 60 months for new-onset dementia., Results: Data from 2,531 participants were analyzed (72.7±6.7 years; range: 60-96 years). Dementia incidence per 1,000 person-years was 15.7 (95% confidence interval, 13.6-18.1). The Youden index determined the cut-off point for dementia incidence, with a conversation index of 16/17 points. The low conversation group included more participants with new-onset dementia. Cox proportional hazards regression crude models showed remarkable relationships between dementia onset and specific conversation measurements, including conversation index. According to the Cox regression adjusted model, the cut-off point of the conversation index showed only a remarkable relationship with dementia onset., Conclusions: Dementia risk was extensively associated with low daily conversation statuses. The assessment of conversational factors may be useful as a risk indicator for the development of Alzheimer's disease and general dementia.

Aim: The present study aimed to examine whether dietary diversity is associated with cognitive impairment, including mild cognitive impairment (MCI), in community-dwelling older Japanese adults., Methods: This cross-sectional study was carried out in a general community setting. MCI and global cognitive impairment (GCI) were assessed using the Mini-Mental State Examination and National Center for Geriatrics and Gerontology-Functional Assessment Tool, which are multicomponent neurocognitive tests that include memory attention, executive function and processing speed. Dietary diversity was assessed using the diet variety score. The diet variety score assessed the 1-week consumption frequency of 10 food groups, and either 0 or 1 point was allocated to each category based on the following responses: (i) "eat almost every day" (1 point); and (ii) "not eaten almost daily" (0 points). Older adults with a diet variety score of ≥3 points were defined as having high dietary diversity., Results: Data included 8987 older adults (mean age 73.9 ± 5.5 years; men 44.3%). The overall prevalences of MCI and GCI were 17.1% (n = 1538) and 8.4% (n = 753), respectively. The proportion of patients with a high dietary diversity was 69.9% (n = 6286). Multinomial logistic regression analysis revealed high dietary diversity was associated with MCI (OR 0.83, 95% CI 0.73-0.94) and GCI (OR 0.77, 95% CI 0.65-0.92) after adjusting for covariates., Conclusions: This study had a large sample size of older Japanese adults, and showed that high dietary diversity was associated with a lower proportion of MCI and GCI among older adults. Geriatr Gerontol Int 2024; 24: 75-81., (© 2023 Japan Geriatrics Society.)

Background: Sarcopenia is a clinical issue in older adults that leads to serious adverse health outcomes, including disability. The present study investigated whether dietary diversity affects the incidence of disability in older adults with sarcopenia., Method: Participants were 759 Japanese older adults with sarcopenia (mean age 77.2 ± 6.0 years; 44.4 % men) who were aged ≥65 years at the time of the examination. Sarcopenia was diagnosed according to the recommendations of the European Working Group on Sarcopenia in Older People 2. Dietary diversity was assessed using a diet variety score. This diet variety score assessed the one-week consumption frequency of ten food groups, according to the following responses: "eat almost every day" (1 point), or "not eaten almost daily" (0 points). Older adults with a diet variety score of 3 or more points were defined as having high dietary diversity. Incident disability was certified by long-term care insurance (mean follow-up duration 32 months)., Results: The cumulative disability incidence rates in the older adults with low dietary diversity and high dietary diversity were 23.3 % and 16.9 %, respectively. Cox proportional hazards regression analysis revealed high dietary diversity was associated with a lower risk of incident disability in older adults with sarcopenia (hazard ratio 0.66, 95 % confidence interval 0.47-0.92; p = 0.015), after adjusting for covariates., Conclusions: This longitudinal study revealed that high dietary diversity is associated with a lower risk of incident disability among sarcopenic Japanese older adults., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To examine the associations of a combination of urinary incontinence (UI) and life-space activity/mobility with the risk of incident disability among community-dwelling older adults., Study Design: The participants were 12,808 older adults for the cross-sectional study and 12,516 older adults who completed the follow-up assessment., Main Outcome Measures: UI was assessed using a questionnaire. Life-space activity/mobility was evaluated using total, physical, and social scores on the Active Mobility Index (AMI). Participants were classified into four groups (high AMI total score + no UI; high AMI total score + UI; low AMI total score + no UI; low AMI total score + UI). Incident disability was extracted from the Japanese Long-Term Care System., Results: During the 24-month follow-up, 562 participants (4.5 %) developed disability. Those with a low AMI score + no UI (hazard ratio, 1.35; 95 % confidence interval, 1.07-1.71) and those with a low AMI score + UI (hazard ratio, 2.00; 95 % confidence interval, 1.56-2.56) had a higher risk of incident disability than those with a high AMI score + no UI in the follow-up analysis., Conclusions: A combination of UI and low AMI score was associated with an increased risk of incident disability, whereas having UI but a high AMI score was not associated with an increased risk of incident disability. Our findings may help identify older adults at high risk of developing disabilities., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The primary aim of this systematic review was to examine the efficacy of driving interventions with regard to a reduction in motor vehicle crashes and improvements in driving skills among older people. The secondary aim was to identify the optimal type (on-road or off-road) and dosage (period, sessions, and duration) of driving interventions for improving driving skills in older people. We searched MEDLINE, EMBASE, PsycINFO, and Scopus of Systematic Reviews for papers published from their inception to December 1, 2020, as well as the reference lists of the included papers. The selected studies were randomized controlled trials examining the effects of driving interventions among community-dwelling older drivers aged 65 years and over. A meta-analysis of two studies (n = 960) showed that driving interventions significantly reduced the number of motor vehicle crashes per person-years. Ten studies (n = 575) were included in the meta-analysis showing that the interventions significantly improved the driving skill scores. Driving skill scores significantly improved after on-road training, and in interventions of at least 3 h, 3 sessions, and 3 weeks. Driving interventions significantly improve driving skills and reduce motor vehicle crashes among older drivers aged 65 years and over. On-road training is more efficacious than off-road training and driving interventions of at least 3 h taking place in 3 sessions over a period of 3 weeks may be required to improve driving skills in older drivers. Geriatr Gerontol Int 2023; 23: 771-778., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Objectives: Self-monitoring of physical, cognitive, and social activities may be a means of helping older adults to adopt or maintain an active lifestyle, but its effect on disability onset is unknown. This study aimed to examine the association between self-monitoring of the activities and disability onset in older adults., Design: Longitudinal, observational study., Setting and Participants: General community setting. Participants were 1399 older adults aged ≥75 years (mean age: 79.3 ± 3.6 years; 48.1% female)., Methods: Participants conducted self-monitoring of physical, cognitive, and social activities using a specialized booklet and a pedometer. Level of engagement in self-monitoring was assessed based on the percentage of days in a year for which activities were recorded: no-engagement group (0% of days recorded; n = 438), midlevel-engagement group (0.1-89.9% of days recorded; n = 416), and high-engagement group (≥90% of days recorded; n = 545). Disability onset was determined by whether the participants were awarded a long-term care insurance certification over the 2 years after the explanation of the booklet and pedometer., Results: Cox proportional hazard regression models showed that the high-engagement group, when compared to the no-engagement group, had a significantly reduced hazard ratio (HR) for disability onset, after adjustment for covariates (HR 0.54, 95% CI 0.34-0.86, P = .010). After propensity score adjustment through inverse probability of treatment weighting (IPTW) and propensity score matching (PSM), the high-engagement group's HR remained significantly lower (IPTW: HR 0.54, 95% CI 0.34-0.86, P = .010; PSM: HR 0.58, 95% CI 0.35-0.96, P = .032)., Conclusions and Implications: Self-monitoring of physical, cognitive, and social activities reduces the risk of 2-year disability onset in community-dwelling older adults. Further studies in other settings are needed to examine whether self-monitoring of activities can be a population approach for the primary prevention of disability in other settings., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Although overlapping frailty and fear of falling (FoF) are likely to increase with population aging, the combined effect of frailty and FoF on incident disability is not yet well understood., Aims: The purpose of this study is to examine whether frailty combined with FoF increased the risk of incident disability in older adults. Our secondary purpose was to clarify the synergistic effect of frailty and FoF on incident disability., Methods: This is a prospective study. Participants were 9372 older adults (mean age 73.5 years). Frailty status was assessed using the Japanese Cardiovascular Health Study index, and FoF was measured using two closed questions. Incident disability was prospectively monitored by their long-term care insurance records., Results: During the follow-up period (mean duration 23.4 months), 487 (5.2%) participants developed disability. The proportion of incident disability linearly increased according to FoF level regardless of baseline frailty status. Frail participants with FoF had a higher risk of incident disability than those with frailty only or neither (adjusted hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.95-3.54). Frailty in combination with excessive FoF further increased the risk of incident disability (adjusted HR 4.30, 95% CI 2.56-7.23) although no synergistic effect was observed (relative excessive risk due to interaction 1.69, 95% CI - 0.55, 3.93)., Conclusion: The overlapping status of frailty and FoF, especially excessive FoF, increases the risk of incident disability in older adults., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Importance: To prevent motor vehicle collisions by older drivers, the increased risk of collisions should be considered early. Cognitive decline increases the risk of car collisions. Motoric cognitive risk syndrome (MCR), characterized by the presence of cognitive concerns and slow gait, can be assessed conveniently and is useful to assess the risk of dementia., Objective: To examine the association between MCR assessment findings and car collisions among older drivers in Japan., Design, Setting, and Participants: This cross-sectional study used data from a community-based cohort study, the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes, conducted in Japan from 2015 to 2018. Participants were community-dwelling older adults aged at least 65 years. Data were analyzed from February to March 2023., Exposure: MCR was defined as having subjective memory concerns (SMC) and slow gait. Participants were classified into 4 groups: no SMC or slow gait, only SMC, only slow gait, and MCR., Main Outcomes and Measures: Participants were asked about the experience of car collisions during the last 2 years and near-miss traffic incidents during the previous year through face-to-face interviews. Odds of experiencing a collision or near-miss traffic incident were assessed using logistic regression., Results: Among a total of 12 475 participants, the mean (SD) age was 72.6 (5.2) years, and 7093 (56.9%) were male. The group with only SMC and the group with MCR showed a higher proportion of both car collisions and near-miss traffic incidents than the other groups (adjusted standardized residuals > 1.96; P < .001). Logistic regression analysis showed the only SMC and MCR groups had increased odds of car collisions (only SMC group: odds ratio [OR], 1.48; 95% CI, 1.27-1.72; MCR group: OR, 1.73; 95% CI, 1.39-2.16) and near-miss traffic incidents (only SMC group: OR, 2.07; 95% CI, 1.91-2.25; MCR group: OR, 2.13; 95% CI, 1.85-2.45) after adjusting for confounding factors. After stratifying MCR assessments by objective cognitive impairment, significant associations were still observed. In the only slow gait group, objective cognitive impairment was associated with increased odds of car collisions (OR, 1.96; 95% CI, 1.17-3.28)., Conclusions and Relevance: In this cross-sectional study of community-dwelling older drivers in Japan, SMC and MCR were associated with car collisions and near-miss traffic incidents independent from objective cognitive impairment. Future studies should examine the mechanism of these associations in more detail.

Background: In clinical settings, muscle mass and bone mineral density assessments are usually performed using dual-energy X-ray absorptiometry (DXA), the clinical standard technique. However, DXA is often unavailable in community settings. This study aimed to determine whether osteoporosis, osteopenia (OP) and sarcopenia (SP) identified by simplified instruments are associated with the future incidence of disability and mortality and evaluate the validity of these instruments as community screening tools. We also examined osteosarcopenia (OS), defined as the coexistence of OP and SP, as a new indicator of geriatric syndromes to determine whether it has an additive effect on adverse outcome incidence compared with OP and SP alone., Methods: In total, 8995 older adults participated in the study (women: 51.7%, average age: 73.5 ± 5.4 years). Data were extracted from the Japanese national cohort study, National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. We determined OP based on T-scores generated based on the speed of sound, which is the time taken for ultrasound waves to go through a determined distance in the calcaneus bone. Skeletal muscle mass was evaluated using a bioimpedance analysis device. Handgrip strength and walking speed were measured as physical performance indicators. Incidences of disability and mortality were prospectively determined for 5 years., Results: The prevalence of OP, SP and OS was 45.5%, 3.9% and 7.4%, respectively. The incidence of disability in the nonOP/nonSP, OP, SP and OS groups was 6.5%, 14.9%, 20.5% and 33.5%, respectively. The incidence of mortality in the nonOP/nonSP, OP, SP and OS groups was 4.0%, 4.9%, 10.3% and 10.2%, respectively. Participants with OP (hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.25-1.68), SP (HR: 1.38, 95% CI: 1.08-1.76) and OS (HR: 1.73, 95% CI: 1.43-2.09) had a higher risk of disability than nonOP/nonSP participants. Participants with OP (HR: 1.31, 95% CI: 1.04-1.64) and OS (HR: 1.45, 95% CI: 1.05-2.00) had a higher risk of mortality than nonOP/nonSP participants. SP was not significantly related to mortality (HR: 1.14, 95% CI: 0.90-1.45). There was no statistical interaction between OP and SP in incident disability and mortality., Conclusions: Among older adults, OS identified by bioimpedance and quantitative ultrasound assessments was associated with an increased risk of disability and mortality. Further research is needed to implement these findings in community health activities, such as setting precise cut-off values and constructing accurate disability and mortality prediction models., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

The objective of this study was to identify the prevalence of family history of cancer using cohorts participating in the Japanese National Center Cohort Collaborative for Advancing Population Health (NC-CCAPH). We pooled data from seven eligible cohorts of the Collaborative with available data on family history of cancer. Prevalence of family history of cancer and corresponding 95% confidence intervals are presented for all cancers and selected site-specific cancers for the total population and stratified by sex, age, and birth cohort. Prevalence of family history of cancer increased with age ranging from 10.51% in the 15 to 39 year age category to 47.11% in 70-year-olds. Overall prevalence increased in birth cohorts from ≤ 1929 until 1960 and decreased for the next two decades. Gastric cancer (11.97%) was the most common site recorded for family members, followed by colorectal and lung (5.75%), prostate (4.37%), breast (3.43%) and liver (3.05%) cancer. Women consistently had a higher prevalence of family history of cancer (34.32%) versus men (28.75%). Almost one in three participants had a family history of cancer in this Japanese consortium study highlighting the importance of early and targeted cancer screening services., (© 2023. The Author(s).)

Objectives: The aim of this study was to examine whether dietary diversity is associated with sarcopenia in community-dwelling older Japanese adults., Methods: We used a cross-sectional large cohort data set from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Data from 9080 older adults (mean age 74 ± 5.6 y; 44.4% were men) were included in this cross-sectional study. Sarcopenia was assessed using muscle mass, muscle strength, and physical performance represented by gait speed. We assessed 1-wk consumption frequency of food types, including meat, fish/shellfish, eggs, milk, soybean products, green and yellow vegetables, potatoes, fruits, seaweeds, fats, and oil. Consumption frequency was allotted to each category for the following responses: eat almost every day, eat 3 or 4 /wkd, eat 1 or 2 d/wk, and hardly ever eat. Poor dietary diversity was defined as those who responded hardly ever eat for any of the 10 foods., Results: This study revealed that 2647 participants (29.2%) had poor dietary diversity. Poor dietary diversity was associated with confirmed sarcopenia (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08-1.96) and severe sarcopenia (OR, 1.58; 95% CI, 1.08-2.39). Furthermore, poor dietary diversity of low-protein foods was significantly associated with sarcopenia (OR, 1.57; 95% CI, 1.13-2.20) as well as poor dietary diversity of high-protein foods (OR, 1.47; 95% CI, 1.12-1.92)., Conclusions: This cross-sectional study revealed that poor dietary diversity was associated with sarcopenia among older adults. Ingestion of low-protein foods and high-protein foods is infrequently associated with sarcopenia and ingestion of high-protein foods., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Active mobility index (AMI) is a questionnaire to assess going-out behavior with physical and social activity. The association between AMI scores and objectively measured physical activity (PA) in older adults is unknown., Methods: Community-dwelling older adults aged ≥ 70 years participated in an examination and wore a triaxial accelerometer for seven or more days. The accelerometer measured the time of moderate-to-vigorous intensity PA (MVPA) and light intensity PA (LPA), and step counts. The AMI assessed life space (distance from the respondent's home: < 1, 1-10, or > 10 km) and related activities during the previous month. The AMI total, physical, and social scores were calculated., Results: The analyzed data were 2499 participants (mean age: 75.5 ± 4.0 years; 54.4% female). Comparing PA among quartile groups of each AMI score, higher AMI total and physical score groups were associated with higher MVPA, LPA, and step counts (all P < 0.01). The Q4 group of AMI social scores showed significantly higher LPA and step counts than the Q1 and Q2 groups (P < 0.01). The logistic regression model showed higher score groups of AMI total and physical scores associated with increased adjusted odds ratio (aOR) of meeting recommended PA, ≥ 150 min/week of MVPA., Conclusions: Older adults with higher AMI total and physical scores, engaged in more PA. Future studies can use the present findings when estimating PA in older adults from AMI scores and examining the association between AMI scores and health outcomes., (© 2022. The Author(s).)

Objectives: Diabetes mellitus (DM) is associated with risk of sarcopenia. However, whether glycated hemoglobin (HbA1c) levels are associated with sarcopenia has not reached a consensus. The purpose of this study was to examine the association between diabetes status based on HbA1c levels and sarcopenia indices in community-dwelling older adults stratified by body mass index (BMI) status., Design: An observational cross-sectional study., Setting and Participants: General community setting. The participants were 18,940 community-dwelling older adults (mean age 73.7 ± 5.7 years, 45.0% men)., Methods: According to their medical history for diabetes mellitus and blood HbA1c levels the participants were classified into the control group (no DM history and HbA1c ≤5.6%), pre-DM group (no DM history and HbA1c 5.7%-6.4%), or DM group (DM history or HbA1c ≥6.5%). For assessments of sarcopenia, muscle mass and muscle strength were measured based on the clinical definition., Results: A multiple logistic regression analysis showed that the DM group did not have a clear association with sarcopenia [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.82-1.38] or low muscle mass (OR 1.15, 95% CI 0.94-1.39), and was associated with low muscle strength (OR 1.21, 95% CI 1.08-1.36) in the adjusted model including BMI. There was a positive correlation between BMI and skeletal muscle index (r = 0.57, P < .001). Stratified by BMI, the DM group was associated with low muscle mass among the underweight participants (OR 1.87, 95% CI 1.03-3.39), and low muscle strength among the overweight participants (OR 1.22, 95% CI 1.04-1.43)., Conclusions and Implications: Diabetes status was associated with low muscle mass and low muscle strength, and the association depended on BMI. Our findings could be helpful for identifying older adults with a high risk of sarcopenia, although further study is needed., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Inflammation may play a role in Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome comprised of slow gait and cognitive complaints. Our objective was to examine associations of inflammatory biomarkers with MCR., Methods: We examined association of interleukin-6 (IL-6) and C-reactive protein (CRP) with prevalent MCR using logistic regression in 3,101 older adults (52% female) from five cohorts (National Center for Geriatrics & Gerontology Study of Geriatric Syndromes [NCGG-SGS], Central Control of Mobility in Aging [CCMA], Tasmanian Study of Cognition and Gait [TASCOG], LonGenity, and Einstein Aging Study [EAS]). Associations were reported as odds ratios adjusted for sex, age, education, depressive symptoms, body mass index, and vascular diseases (aOR) with 95% confidence intervals (CI). Meta-analysis and analyses stratified by vascular disease were also done., Results: Although associations between higher (worse) CRP and IL-6 tertiles and MCR were only seen in three out of the five cohorts (EAS, TASCOG, and LonGenity), when a pooled meta-analysis was performed, a robust association was demonstrated. In meta-analysis, highest tertiles of IL-6 (aOR 1.57, 95%CI 1.01- 2.44) and CRP (aOR 1.65, 95%CI 1.09-2.48) was associated with MCR versus lowest tertiles in the pooled sample. Higher CRP was associated with MCR among those with vascular disease in TASCOG and LonGenity cohorts, and among those without vascular disease in EAS., Conclusions: IL-6 and CRP levels are associated with MCR in older adults, and this association varies by presence of vascular disease., Competing Interests: The authors report no disclosures relevant to the manuscript., (© 2022 The Authors. Published by Elsevier B.V.)

Although clinical trials have reported an improvement in the prognosis of hemophagocytic lymphohistiocytosis (HLH), current treatment outcomes are unsatisfactory, especially in severe cases. Most clinical trial patients with severe disease discontinue participation due to complications associated with HLH or treatment-related toxicity. A retrospective survey of patients who discontinued participation in the JPLSG HLH-2004 clinical trial was conducted to review the detailed course of these cases to optimize HLH treatment and supportive care. Findings in these patients were compared with those of 45 patients who completed the protocol treatment. The 3 year overall survival rate of patients who completed treatment was 86.7%, versus 50.7% for those who did not complete treatment. Incidence of serious adverse events, such as infections, coagulopathy, and posterior reversible encephalopathy syndrome, during the initial 8 weeks of treatment was much higher in patients who did not complete treatment than in patients who completed treatment. To improve overall outcomes of patients with HLH, it is important to not only optimize HLH-directed therapy but also provide appropriate supportive care., (© 2022. Japanese Society of Hematology.)

Background: The motoric cognitive risk syndrome (MCR) was characterized by slow gait and subjective cognitive complaints. MCR was associated with brain structural changes. However, the association between white matter hyperintensities (WMH) and MCR was unclear and the aim of this study was to examine this association., Material and Methods: The study participants were 1227 older adults (mean age: 72.0 ± 6.0 yrs, women: 52.6%). We collected magnetic resonance imaging (MRI) data to assess WMH. To assess MCR, data on gait speed and subjective cognitive complaints were collected. Demographical and medical data was collected as covariates., Results: Among participants, the proportion of MCR was 5.0% (n = 61) and severe WMH was 16.8% (n = 206). From logistic regression analysis, severe WMH associated with MCR even when adjusted for covariates (odds ratio 2.18 [95% confidential interval 1.15-4.16], p = 0.017). This association was observed in subgroups stratified by the participants' characteristics: higher age, not having fall history, not obesity, not being physical inactivity and not having depressive symptom., Conclusions: Our findings revealed that vascular pathophysiological changes in the brain were associated with MCR. The association was pronounced by several factors. Further evaluation was required to clarify pathophysiology of MCR., Competing Interests: None., (© 2022 The Authors. Published by Elsevier B.V.)

Objectives: To develop a questionnaire-based Active Mobility Index (AMI) to assess going-out behavior with physical and social activity among older adults, and to assess the criterion-related and predictive validity of the AMI., Design: Prospective cohort study., Setting and Participants: General community setting. Participants comprised 4432 older adults [mean age: 75.9 ± 4.3 (70-96) years; 2100 men (47.4%)]., Methods: AMI assessed life-space and activities in each life-space (distance from the respondent's home: <1 km, 1-10 km, or >10 km) according to physical or social activity during the past 1 month by noting frequency, purpose, type of transportation, interaction with others, and physical activity. Baseline characteristics and outcomes were compared by AMI score quartiles (highest: Q4). To examine the criterion-related validity of AMI, depressive symptoms, frailty, and cognitive function were assessed. During follow-up, incident disability was monitored by Long Term Care Insurance certification., Results: Lower scores (Q1-Q3 groups) were associated with more depressive symptoms, frailty, and cognitive impairment compared with the Q4 group (all P < .001). Multiple logistic regression analyses revealed significantly higher odds ratios in the Q1 group in all health adverse outcomes compared with the Q4 group [depressive symptoms, odds ratio (OR) 3.94, 95% confidence interval (CI) 2.95-5.28; frailty, OR 3.20, 95% CI 2.31-4.44; cognitive impairment, OR 1.28, 95% CI 1.04-1.57]. Cox proportional hazards modeling indicated that the Q1 group had a higher risk of incident disability compared with the group (hazard ratio 1.53, 95% CI 1.24-1.88)., Conclusions and Implications: AMI to assess life-space with physical and social activity among older people was associated with depressive symptoms, frailty, and cognitive impairment. Lower AMI scores were associated with higher incident disability risk. Further studies are needed to elucidate whether AMI is causally associated with incident adverse health outcomes., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: A physically active lifestyle, including physical and social activities, is needed to maintain muscle mass, strength, and physical performance. A large life space characterizes an active lifestyle, but the association between life space with physical and social activities and sarcopenia is unclear. This study aimed to examine the association between life space with physical and social activities, assessed using the Active Mobility Index (AMI), and sarcopenia in community-dwelling Japanese older adults., Methods: This study used a large, cross-sectional cohort dataset from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes (NCGG-SGS). Between 2013 and 2018, community-dwelling Japanese adults aged ≥60 years participated in the NCGG-SGS. Sarcopenia was identified by measuring muscle mass and strength based on the clinical definition. The secondary outcomes were sarcopenia indices, including lower muscle mass, lower muscle strength, and lower gait speed. AMI assessed life space with physical and social activities in each life space (distance from the respondent's home: <1, 1-10, or >10 km) during the past month by noting the frequency, primary purpose, type of transportation, interaction with others, and physical activity. The associations between quartile groups of AMI total, physical, and social scores and sarcopenia were examined using a logistic regression model., Results: From all participants, 21 644 participants (age 73.5 ± 5.8 years, 54.7% female) were included in the analysis. The prevalence of sarcopenia was 4.1% (n = 894). For the AMI total score, referred to Q1 group, Q3 and Q4 groups were significantly associated with a reduced odds ratio (OR) of sarcopenia after adjusting for all covariates [adjusted OR (aOR) (95% confidence interval), Q3: 0.71 (0.57-0.89), Q4: 0.69 (0.55-0.87)]. Q3 and Q4 of the AMI physical score groups were also significantly associated with reduced OR of sarcopenia [Q3: 0.71 (0.57-0.89), Q4: 0.67 (0.54-0.84)]. For the AMI social score, only the Q4 group showed reduced OR for sarcopenia [0.79 (0.62-1.01)]. Q3 and Q4 of the AMI total score and physical score were associated with reduced OR of all sarcopenia indices (aOR 0.55-0.82, all P < 0.05), whereas Q4 of AMI social score was associated with all indices (aOR 0.85-0.81, all P < 0.05)., Conclusions: The extent of life space with physical activity was associated with sarcopenia in community-dwelling older adults. A longitudinal study is needed to examine whether life space with physical and social activities affect the development of sarcopenia., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

This study aimed to develop a questionnaire for evaluating total sedentary time (ST) and ST with cognitive activity, and to examine the association between ST and cognitive function among Japanese older adults. The questionnaire to evaluate ST comprised 12 items regarding behavior in specific settings, including 8 items on ST with cognitive activity, in a usual week. Older adults aged ≥75 years who participated in a health check-up assessing cognitive function completed the developed questionnaire and subsequently wore an accelerometer and recorded a diary of ST with cognitive activity for a week as validity measures. Cognitive function was assessed with neuropsychological tests covering 4 domains: memory, attention, executive function, and processing speed. Fifty-two participants were included in the validity analysis. Spearman's correlation coefficient indicated fair-to-good agreement between the questionnaire-measured and the diary-measured time for ST with cognitive activity (r = 0.59, p < 0.001), but this was not the case for total ST. Bland-Altman plots showed that the questionnaire-measured total ST contained proportional bias (r = 0.51, p < 0.001). Multiple regression analysis (n = 49) showed longer questionnaire-measured ST with cognitive activity was significantly associated with better neuropsychological test scores (attention: β = -0.38, p = 0.025; executive function: β = -0.46, p = 0.003; and processing speed: β = 0.31, p = 0.041), while total ST was not associated with better cognitive performance. The developed questionnaire showed acceptable validity to measure ST with cognitive activity, which was found to be protectively associated with cognitive function.

Introduction: The aim of this study was to investigate whether the association between driving status and disability in older adults depends on social frailty., Methods: This is a prospective study in a community setting. Participants were surveyed baseline conditions of social frailty and driving status (n = 4642, mean age: 71.7 years). Social frailty was defined according to criteria: going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone every day. Incident disability was prospectively followed up by their long-term care insurance records., Results: Of the participants, 3348 (72.1%) were current drivers. The occurrence of the social frail group, including pre-frail and frail conditions, was higher in the not driving group (55.3%) than the driving group (40.5%). The follow-up period was 60 months (mean: 56.0 months), during which 105 participants (2.3%) died, 58 participants (1.2%) moved out of the city, and 541 participants (11.7%) had incident disability. Both driving status and social frailty were associated with incident disability adjusted for covariates (not driving: hazards ratio [HR] 1.31, 95% confidence interval [CI] 1.06-1.32; social frailty: HR 1.40, 95% CI 1.17-1.67). Driving status was associated with incident disability in the social frail group (not driving: HR 1.35, 95% CI 1.03-1.77) but not in the non-social frail group (not driving: HR 1.23, 95% CI 0.86-1.74)., Conclusions: Not driving and social frailty were independently associated with disability. Further, the association between driving status and disability depended on social frailty., (Copyright © 2021 Elsevier B.V. All rights reserved.)

IKAROS and CTLA4 deficiencies are inborn errors of immunity and show similar clinical phenotypes, including hypogammaglobulinemia and autoimmune diseases (ADs). However, the differences in clinical features and pathogenesis of these are not fully understood. Therefore, we performed systematic literature reviews for IKAROS and CTLA4 deficiencies. The reviews suggested that patients with IKAROS deficiency develop AD earlier than hypogammaglobulinemia. However, no study assessed the detailed changes in clinical manifestations over time; this was likely due to the cross-sectional nature of the studies. Therefore, we conducted a retrospective longitudinal study on IKAROS and CTLA4 deficiencies in our cohort to evaluate the clinical course over time. In patients with IKAROS deficiency, AD and hypogammaglobulinemia often develop in that order, and AD often resolves before the onset of hypogammaglobulinemia; these observations were not found in patients with CTLA4 deficiency. Understanding this difference in the clinical course helps in the clinical management of both. Furthermore, our results suggest B- and T-cell-mediated ADs in patients with IKAROS and CTLA4 deficiencies, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoshino, Toyofuku, Mitsuiki, Yamashita, Okamoto, Yamamoto, Kanda, Yamato, Keino, Yoshimoto-Suzuki, Kamizono, Onoe, Ichimura, Nagao, Yoshimura, Tsugawa, Igarashi, Mitsui-Sekinaka, Sekinaka, Doi, Yasumi, Nakazawa, Takagi, Imai, Nonoyama, Morio, Latour and Kanegane.)

Introduction: A cutoff speed of 1.0 m/s for walking at a comfortable pace is critical for predicting future functional decline. However, some older adults with walking speeds below the cutoff point maintain an independent living. We aimed to identify specific predictors of disability development in older adults with slow walking speeds in contrast to those with a normal walking speed., Methods: This prospective cohort study on 11,987 community-dwelling independent Japanese older adults (mean age, 73.6±5.4 years) was conducted between 2011 and 2015. Participants were classified into slow walking speed (comfortable walking speed slower than 1.0 m/s) and normal walking speed (speed of 1.0 m/s or faster) groups and followed up to assess disability incidence for 24 months after baseline assessments. Cox proportional hazards regression models were used to identify predictors of disability development in the slow and normal walking groups., Results: Overall, 26.7% of participants had a slow walking speed. At follow-up, 11.3% and 2.7% of participants in the slow and normal walking groups, respectively, developed disability (p < 0.01). Cox regression models revealed that age (hazard ratio 1.08, 95% confidence interval 1.06-1.11), walking speed (0.10, 0.05-0.20), grip strength (0.97, 0.95-0.99), Parkinson's disease (4.16, 2.05-8.44), and Symbol Digit Substitution Test (SDST) score (0.98, 0.96-1.00) were significantly associated with disability incidence in the slow walking group. In the normal walking group, age, grip strength, cognition, 15-item Geriatric Depression Scale (GDS) score, and reduced participation in outdoor activity were significantly associated with disability incidence; however, there was no significant association with walking speed., Conclusions: Decreased walking speeds have considerably greater impact on disability development in older adults with a slow walking speed than in those with a normal walking speed. Health-care providers should explore modifiable factors for reducing walking speed; they should also encourage improvement of risk factors such as muscle weakness and depression to reduce disability risk in older adults with slow walking speeds., (© 2021 S. Karger AG, Basel.)

Objective: This study aims to estimate the cost-effectiveness of combined physical and cognitive programs designed to prevent community-dwelling healthy young-old adults from developing dementia., Methods: The analysis was conducted from a public healthcare and long-term care payer's perspective. Quality-adjusted life years (QALYs) and expenses for health services and long-term care services were described in terms of effectiveness and cost, respectively. A thousand community-dwelling healthy adults aged 65 years were generated through simulation and analyzed. The incremental cost-effectiveness ratio (ICER) of adults with preventive program intervention compared to those with nonintervention was simulated with a 10-year cycle Markov model. The data sources for the parameters to build the Markov models were selected with priority given to higher levels of evidence. The threshold for assessing cost-effectiveness was set as less than 5,000,000 Japanese yen/QALY., Results: The ICER was estimated as -5,740,083 Japanese yen (US$-57,400)/QALY., Conclusion: A program targeting community-dwelling healthy young-old adults could be cost-effective., (©2022 Japanese Society of Physical Therapy.)

Introduction: This study aimed to examine the prospective association between computer use and cognitive decline among community-dwelling Japanese older adults, considering the characteristics of computer users., Methods: This four-year prospective cohort study was conducted in Obu, Japan. Participants who were cognitive intact at Wave 1 (2011-2012) were followed through the study period. Cognitive decline was defined as scoring below the standard threshold in at least one of four neuropsychological tests at Wave 2 (2015-2016). The association between computer use at Wave 1 and cognitive decline was examined using logistic regression for complete samples (n = 2010, 52.5% female, mean 71.0 ± 4.7 years) and imputed samples (n = 3435, 51.8% female, mean 71.5 ± 5.3 years)., Results: The computer use group had a reduced adjusted odds ratio (aOR) of cognitive decline, after adjustment for covariates, in both the complete and imputed samples (complete samples: aOR 0.71, 95% confidence interval [CI] 0.52-0.97, p = 0.030; imputed samples: aOR 0.67, 95% CI 0.51-0.88, p < 0.003). Stratified analysis of both samples showed that computer users with ≥ 10 years' education, a GDS score of < 6, or a walking speed of ≥ 1.0m/s, showed reduced aOR for cognitive decline (aOR 0.61 to 0.69, p < 0.05). Those with < 10 years of education years, GDS scores ≥ 6 of GDS, or walking speed < 1.0m/s did not show significant association., Conclusion: Computer use is longitudinally associated with protected cognitive function, based on computer user characteristics., (Copyright © 2021. Published by Elsevier B.V.)

Aim: Physical frailty is a critical health problem that can increase the risk of adverse health outcomes in older adults. Driving cessation has been associated with negative outcomes such as disability. However, the relationship between physical frailty and driving cessation remains unclear. Thus, this study aimed to examine whether driving cessation is associated with physical frailty transition in community-dwelling older adults., Methods: This prospective cohort study was performed in a community setting in Japan. Participants were 2934 older Japanese adults, classified into two groups according to their driving status: a driving group (drivers at baseline who continued driving at a 4-year follow-up) and a driving cessation group (drivers at baseline who ceased driving by 4-year follow-up). We examined the association between physical frailty transition and driving cessation over a 4-year period, using logistic regression analysis before and after imputation., Results: In total, 3.9% of community-dwelling older adults had ceased driving by the 4-year follow-up. Rates for physical frailty transition in the driving and driving cessation groups were 4.6% and 17.1%, respectively (P < 0.001). In fully adjusted logistic regression analysis, when compared with driving, driving cessation independently affected physical frailty transition. The results were similar after multiple imputations., Conclusions: Our findings indicated driving cessation was an independent risk factor associated with physical frailty transition in older adults. As physical frailty in older adults can contribute to negative health outcomes, including increased disability and mortality, preventing frailty has important public health implications. Geriatr Gerontol Int 2021; 21: 1047-1052., (© 2021 Japan Geriatrics Society.)

Background: This cross-sectional study aimed to investigate the relationship of the ACTN3 genotype with thigh muscle volume and physical performance in older adults with sarcopenia or pre-sarcopenia., Methods: Data from 64 older Japanese adults (mean age 74.4 ± 6.9 years, women 71.9%) with sarcopenia or pre-sarcopenia were analyzed. Sarcopenia and pre-sarcopenia were defined using the Asian Working Group for Sarcopenia. We collected oral mucosa samples to determine the ACTN3 genotype. Thigh muscle volumes were measured using magnetic resonance imaging. Physical performance was assessed using the usual and maximum gait speed, timed up and go test, and five-repetition sit-to-stand test. Muscle strength was assessed using grip strength., Result: The ACTN3 genotype proportions were 20.3% for RR, 51.6% for RX, and 28.1% for XX. Participants with the RR genotype showed greater thigh muscle volume/ht 2 compared to those with the RX and XX ACTN3 genotypes (p < 0.05). The multiple linear regression analysis revealed that RX (p < 0.01) and XX (p < 0.01) ACTN3 genotypes, compared to RR, were associated with lower thigh muscle volume/ht 2 and with age, sex (reference; men), weight and maximum walking speed. There was no significant difference between physical performance and muscle strength between the ACTN3 genotypes., Conclusion: The ACTN3 genotype of the X allele was associated with decreased thigh muscle volume compared to the ACTN3 genotype of RR in older adults with sarcopenia or pre-sarcopenia., (Copyright © 2021. Published by Elsevier Inc.)

Gait is one of the best measures of physical function in older adults. The study examined the association between spatiotemporal gait variables and mortality among older adults. The participants were 4,298 older adults in the National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes. At baseline we measured the following spatiotemporal gait variables: gait speed, stride length, cadence, and stride length variability. Demographic variables, medical conditions, cognitive function, and physical inactivity were also assessed at baseline. We obtained gait measurements over five trials using an electronic gait-measuring device mounted at the middle 2.4 m section of a 6.4 m straight and flat pathway, with 2 m allowed for acceleration and deceleration. Participants' usual gait speed was measured. Subsequent incident death was confirmed using administrative data. During follow-up (mean duration: 1,571 days), there were 185 incident deaths among participants. Low function on all gait variables increased risk of mortality (adjusted hazard ratio [95% confidence interval], gait speed: 1.83 [1.31-2.56], stride length: 1.85 [1.31-2.62], cadence: 1.60 [1.17-2.18], stride length variability: 1.50 [1.09-2.06]). In addition, mortality risk increased with the number of variables showing low gait function compared with normal gait function (p < .05). Slower gait speed, shorter stride length, lower cadence, and higher stride length variability were associated with increased mortality. Multifaceted gait analysis could be useful for evaluating mortality risk., (Copyright © 2021. Published by Elsevier B.V.)

Background: This study aimed to examine whether physical activity measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) can predict incident disability in Japanese older adults., Methods: Community-dwelling older adults participated in a prospective cohort survey. The time spent in moderate- to vigorous-intensity physical activity was assessed at the survey baseline using the IPAQ-SF. The participants were categorized into those who spent ≥150 minutes per week (physically active) or <150 minutes per week (physically inactive) in moderate- to vigorous-intensity physical activity. Incident disability was monitored through Long-Term Care Insurance certification during a follow-up lasting 5 years., Results: Among the 4387 analyzable participants (mean age = 75.8 y, 53.5% female), the IPAQ-SF grouped 1577 (35.9%) and 2810 (64.1%) participants as those who were physically active and inactive, respectively. A log-rank test showed a significantly higher incidence of disability among the inactive group of participants (P < .001). The Cox proportional hazards model showed that physically inactive participants had a higher risk of incident disability than the physically active ones did, even after adjusting for covariates (hazard ratio, 1.24; 95% CI, 1.07-1.45, P < .001)., Conclusions: Older adults identified as physically inactive using the IPAQ-SF had a greater risk of developing disabilities than those identified as physically active. The IPAQ-SF seems to be appropriate to estimate the incidence risk of disability.

Background: Identifying factors that contribute to the development of sarcopenia in older adults is a public health priority. Although several studies have examined the association between sleep duration and sarcopenia, additional evidence is needed to reveal the causality of this association, especially from a longitudinal study. The purpose of the present study was to examine whether sleep duration was associated with the progression to sarcopenia and its subcomponents among community-dwelling older adults in Japan., Methods: A total of 3918 older community-dwelling people (mean age: 73.2 ± 6.0 years, 51.8% female) included in the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes were analysed. Sleep duration was assessed using a self-reported questionnaire. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of progression of sarcopenia at Wave 2 (4 years later), according to the three categories of sleep duration [short: ≤6.0 h, medium: 6.1-8.9 h (control), & long: ≥9.0 h)] at Wave 1., Results: The numbers in each group in the second wave among the total sample were as follows: short 403 (10.3%), medium 2877 (73.4%), and long 638 (16.3%). Significant associations with the progression of sarcopenia were found in the long sleep duration group compared with the medium one, even after adjustment for other covariates (OR 1.66, 95% CI: 1.02-2.69, P = 0.040). Long sleep duration was significantly associated with slow gait (OR: 1.55, 95% CI: 1.17-2.06, P = 0.002) and low grip strength (OR: 1.34, 95% CI: 1.00-1.78, P = 0.047) but was not associated with low muscle mass (OR: 1.33, 95% CI: 0.74-2.38, P = 0.343)., Conclusions: This study revealed that long sleep duration was associated with an increased risk of progression to sarcopenia among older adults., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)