Association between willingness to exercise and incident disability in older adults: a prospective longitudinal cohort study.

PURPOSE: To investigate whether the willingness to exercise (WTE) and exercise habits affect the incidence of disability among older adults. METHODS: This study included 8,354 individuals (72.5 ± 6.2 years, 55.9% female). The participants were divided into three categories based on their WTE: unwillingness to exercise, willingness to exercise (but without exercise habits), and exercise habits. The incidence of disability was prospectively determined within 24 months of the follow-up. Cox regression analysis was used to examine the relationship between WTE and the incidence of disability. RESULTS: Overall, 600 (7.2%), 4,703 (56.3%), and 3,051 (36.5%) participants were classified as unwillingness to exercise, willingness to exercise, and exercise habits, respectively. Compared with the unwillingness to exercise group, the willingness to exercise group (hazard ratio [HR] 0.71, 95%Confidence Interval [CI] 0.52-0.96) and the exercise habits group (HR 0.65, 95%CI 0.46-0.92) had a lower risk of disability incidence. CONCLUSIONS: These results suggest that WTE reduces the risk of disability in older adults. Therefore, the importance of increasing WTE to prevent the occurrence of disabilities is clear. Our results suggest that even though physical activity declines with age, it is important to have the desire to exercise and develop exercise habits.

Discovering Subtypes with Imaging Signatures in the Motoric Cognitive Risk Syndrome Consortium using Weakly-Supervised Clustering.

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.

Study protocol of the safe driving program for the prevention of car accidents: A randomized controlled trial protocol.

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; ••: ••-••.

Associations between Japanese calligraphy practice and sleep quality in community-dwelling older adults: A cross-sectional Study.

Background: Sleep disturbances, such as insomnia, are common among the elderly population and have been associated with negative health outcomes. Japanese calligraphy is a traditional art practice previously associated with various health benefits, such as stress reduction and improved cognitive function; however, its association with sleep quality has not been fully explored. Methods: This cross-sectional study included 21,207 subjects with basic attributes, health status, depressive symptoms, artistic practices, and sleep habits. Individuals who satisfied the chronic insomnia criteria were categorized into the following subtypes: sleep onset latency (SOL) insomnia, early morning awakening (EMA) insomnia, and wake after sleep offset (WASF) insomnia. The t-test, chi-square test, and logistic regression analysis were used to determine the association between Japanese calligraphy practice and sleep quality. Results: In this study, 17,597 elderly Japanese individuals were included, among whom 13.7 % practiced Japanese calligraphy. Regarding sleep characteristics, 32.0 % had chronic insomnia, 13.1 % had SOL insomnia, 9.1 % had EMA insomnia, and 14.2 % had WASF insomnia. Japanese calligraphy practice was associated with lower rates of chronic insomnia (odds ratio [OR] = 0.85, 95 % confidence interval (CI) = 0.76-0.95), including SOL insomnia (OR = 0.84, 95 % CI = 0.71-0.98), and EMA insomnia (OR = 0.80, 95 % CI = 0.66-0.97) but had no significant association with WASF insomnia. Conclusions: This study suggests that Japanese calligraphy practice is associated with lower odds of insomnia, particularly SOL and EMA insomnia. Calligraphy may be an effective nonpharmacological intervention for insomnia and poor sleep quality among elderly Japanese individuals.

Prevalence and Prognostic Impact of Multiple Frailty Domain in Japanese Older Adults.

OBJECTIVES: In this observational study, we aimed to evaluate the independent and overlapping effects of multiple frailty domains on long-term care insurance (LTCI) use. DESIGN: Population-based cohort design. SETTING AND PARTICIPANTS: In total, 9804 community-dwelling older adults were recruited from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. METHODS: The physical domain of frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria. The cognitive domain of frailty was identified as impairment of memory, attention, executive function, or processing speed using standardized thresholds established for each domain in population-based cohorts. The social domain was operationalized using the National Center for Geriatrics and Gerontology-Social Frailty Scale. The use of LTCI was prospectively determined over 60 months using data extracted from the Japanese long-term care insurance system. RESULTS: The data from 7745 participants were analyzed, of whom 793 (10.2%) required LTCI certification within 60 months (interquartile range: 60-60 months). The Kaplan-Meier curve analysis demonstrated that a high number of frailty domains was associated with incident LTCI use. The proportions of incident LTCI use were 6.0%, 12.4%, 30.1%, and 43.9% for non-frail participants and those with impairments in 1, 2, and 3 frailty domains, respectively. In the multivariate Cox regression model, physical, cognitive, and social domain impairments independently increased the risk of incident LTCI use [physical domain impairment, hazard ratio (HR), 1.67; 95% CI, 1.39-2.01; cognitive domain impairment, HR, 1.59; 95% CI, 1.37-1.84; social domain impairment, HR, 1.26; 95% CI, 1.05-1.50]. CONCLUSIONS AND IMPLICATIONS: Overlapping frailty domains were strongly associated with incident LTCI use among community-dwelling older adults. These findings emphasize the importance of assessing multiple frailty domains and tailoring interventions according to the unique circumstances of older adults to prevent functional disabilities.

Validation of the Optimal University of California Los Angeles Loneliness Scale Cutoff Score in Screening for the Prevention of Disability Occurrence Among Older Japanese Adults.

OBJECTIVES: The association between loneliness and disability is a growing public health priority. While the University of California Los Angeles Loneliness Scale (UCLA-LS) has been internationally used as an indicator for assessing loneliness, its optimal cutoff point in relation to disability occurrence has not yet been examined. Therefore, we aimed to determine the optimal cutoff point of the UCLA-LS regarding future disability. METHODS: This longitudinal cohort study was conducted in Tokai City, Aichi Prefecture, Japan. Overall, 4536 community-dwelling older adults (age: 73.8 ± 5.5 years; females: 55.2%) were followed up for 2 years. The area under the curve of the receiver operating characteristic analysis was calculated to evaluate the optimal cutoff point of the UCLA-LS in relation to future disability occurrence using the Youden index, which maximized the sensitivity and specificity of the UCLAS-LS. A survival analysis was conducted to test this cutoff value's external validity, using the presence or absence of disability occurrence as the dependent variable. RESULTS: The cutoff score of the UCLA-LS in relation to future disability was 44 points. An association was found between new disability occurrence and loneliness based on this cutoff value (hazard ratio: 1.67, 95% confidence interval: 1.29-2.16). CONCLUSIONS: Although cultural context should be taken into account, the optimal cutoff scores for the loneliness scale related to disability identified in this study may be a useful indicator for early recognition of loneliness as a global public health problem and for promoting social participation as one of the disability prevention strategies.

Detection of neurophysiological markers of cognitive reserve: an EEG study.

Background and objectives: Cognitive reserve (CR) is a property of the brain that allows for better-than-expected cognitive performance relative to the degree of brain change over the course of life. However, neurophysiological markers of CR remain under-investigated. Electroencephalography (EEG) features may function as suitable neurophysiological markers of CR. To assess this, we investigated whether the dorsal attention network (DAN) and ventral attention network (VAN) activities, as measured during resting-state EEG, moderate the relationship between hippocampal volume and episodic memory. Methods: Participants were recruited as part of the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Hippocampal volume was determined using magnetic MRI, and episodic memory was measured using word lists. After testing the effect of hippocampal volume on memory performance using multiple regression analysis, we evaluated the interactions between hippocampal volume and DAN and VAN network activities. We further used the Johnson-Neyman technique to quantify the moderating effects of DAN and VAN network activities on the relationship between hippocampal volume and word list memory, as well as to identify specific ranges of DAN and VAN network activity with significant hippocampal-memory association. Results: A total of 449 participants were included in this study. Our analysis revealed significant moderation of DAN with a slope of ß = -0.00012 (95% CI: -0.00024; -0.00001, p = 0.040), and VAN with a slope of ß = 0.00014 (95% CI: 0.00001; 0.00026, p = 0.031). Further, we found that a larger hippocampal volume was associated with improved memory performance, and that this association became stronger as the DAN activity decreased until a limit of DAN activity of 944.9, after which the hippocampal volume was no longer significantly related to word-list memory performance. For the VAN, we found that a higher hippocampal volume was more strongly associated with better memory performance when VAN activity was higher. However, when VAN activity extended beyond -914.6, the hippocampal volume was no longer significantly associated with word-list memory. Discussion: Our results suggest that attentional networks help to maintain memory performance in the face of age-related structural decline, meeting the criteria for the neural implementation of cognitive reserve.

Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

Distinct Patterns of Brain Atrophy in Amnestic Mild Cognitive Impairment and Motoric Cognitive Risk Syndromes.

INTRODUCTION: Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer's disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI. METHODS: Cross-sectional data from 733 older adults without dementia or disability (M age = 73.6; 45% women) in the multicountry MCR consortium were examined. MCR was defined as presence of slow gait and cognitive concerns. Amnestic MCI was defined as poor episodic memory performance and cognitive concerns. Cortical thickness and hippocampal volumes were quantified from structural MRIs. Multivariate and univariate general linear models were used to examine associations between cortical thickness and hippocampal volume in MCR and aMCI, adjusting for age, sex, education, total intracranial volume, white matter lesions, and study site. RESULTS: The prevalence of MCR and aMCI was 7.64% and 12.96%, respectively. MCR was associated with widespread cortical atrophy, including prefrontal, insular, cingulate, motor, parietal, and temporal atrophy. aMCI was associated with hippocampal atrophy. CONCLUSION: Distinct patterns of atrophy were associated with MCR and aMCI. A distributed pattern of cortical atrophy - that is more consistent with VaD or mixed dementia- was observed in MCR. A more restricted pattern of atrophy - that is more consistent with AD - was observed in aMCI. The biological underpinnings of MCR and aMCI likely differ and may require tailored interventions.

Association between the level of social participation and depressive symptoms among older Japanese adults: a cross-sectional survey.

BACKGROUND: Social participation is recommended for older adults to remain actively involved in daily life. Social participation is a broad concept, ranging from 'interacting with others without doing a specific activity with them' to 'actively contributing to society.' However, previous studies have not taken into account the components of social participation. Depressive symptoms are significant outcomes in older adults. Social participation mitigates these risks owing to its association with reduced mortality and enhanced quality of life. This study aimed to examine the association between the level of social participation and depressive symptoms in community-dwelling older adults. METHODS: We included 17 040 individuals aged ≥65 years. Social participation was categorised into Level 3, interacting with others without doing a specific activity with them; Level 4, engaging in an activity with others; Level 5, helping others; and Level 6, contributing to society, based on a previous study by Levasseur et al. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale. Logistic regression models were used to examine the association between the level of social participation and depressive symptoms. RESULTS: Overall, 15 069 older adults met the inclusion criteria. A higher level of social participation was associated with lower odds ratios (ORs) for depressive symptoms (Level 6 = OR: 0.43, 95% confidence interval (CI): 0.37-0.50; Level 5 = OR: 0.50, 95% CI: 0.41-0.60; and Level 4 = OR: 0.60, 95% CI: 0.52-0.69). Subgroup analyses based on age and sex yielded similar results across all participants. CONCLUSIONS: Among older adults in Japan, a higher level of social participation was associated with lower rates of depressive symptoms. The relationship between depressive symptoms and the levels of social participation may help develop measures to reduce or prevent depressive symptoms in older adults.

Association Between Falls and Social Frailty in Community-Dwelling Older Japanese Adults.

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.

Impact of fat to muscle ratio with risk of disability on community-dwelling Japanese older adults: A 5-year longitudinal study.

PURPOSE: Sarcopenic obesity is a combination of sarcopenia and obesity, which is associated with the onset of disability. Fat to muscle ratio (FMR) is a screening measure that assesses the ratio of muscle mass to fat mass. However, the relationship between the FMR and disability has not been investigated. METHODS: This study included 11,427 community-dwelling older adults aged ≥65 years enrolled in NCGG-SGS (National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes), a national cohort study in Japan. FMR was measured by the bioelectrical impedance analysis and calculated by dividing fat mass by muscle mass. Cox proportional hazard regression analysis adjusted for covariates was used to investigate the association between FMR and the risk of developing new care needs at 5 years. FMR was divided by about quintile, with quintile 5 as the high. RESULTS: The high FMR group had the highest incidence of disability at 20.8 % for women and 20.1 % for men. In women, the association between FMR and disability was significantly different for the FMR (hazard risk [HR]: 1.43, 95 % confidence interval [CI]: 1.16-1.75). There was no association between FMR and disability in men (HR: 0.98, 95 %CI: 0.76-1.25). Lagged analyses accounting for reverse causality did not change the relationship. CONCLUSIONS: FMR is associated with increased risk of disability in women community-dwelling older adults but not among men. Because the rate of decreased muscle strength is faster in men than in women, early decreased muscle strength may affect men's risk of disability more than muscle mass or fat mass.

Association between physical, cognitive, and social activities with the incident of sarcopenia among community-dwelling older adults: a 4-year longitudinal study.

PURPOSE: The purpose of the present study was to comprehensively examine the association between inadequate physical activity (PA), cognitive activity (CA), and social activity (SA) and the development of sarcopenia. METHODS: We conducted a two-wave survey. In the first-wave survey, we asked participants five questions for each of the three categories-PA, CA, and SA. The low-activity group was defined as those who fell into the decline category for one or more of the five questions. In both Wave 1 and Wave 2, we assessed the sarcopenia status of our participants. The revised definition of the European Working Group on Sarcopenia in Older People 2 was used to determine sarcopenia, and the Asian Working Group for Sarcopenia criteria were used for cut-off points for muscle mass, grip strength, and walking speed. RESULTS: In the second wave, we were able to follow 2,530 participants (mean age 75.0 ± 4.7 years, 47.8% men). A multivariable logistic regression showed that low-PA participants face a higher risk of incident sarcopenia, both before and after multiple imputations (odds ratio [OR] 1.62, 95% confidence interval (CI) 1.22-2.15 before imputation; OR 1.62, 95% CI 1.21-2.18 after imputation); the low-SA group also showed a higher risk of incident sarcopenia both before and after multiple imputations (OR 1.31, 95% CI 1.05-1.64 before imputation; OR 1.33, 95% CI 1.07-1.65 after imputation). CONCLUSION: Each low PA and SA independently led to incident sarcopenia late in life. Encouraging not only PA, but also SA, may be effective to prevent sarcopenia among older adults.

Association between social isolation and diversity in food intake by gender in community-dwelling older adults: A cross-sectional study.

AIM: Few studies have investigated the relationship between low dietary variety and clearly defined social isolation by gender. This study explored the association between dietary variety and social isolation, classified by operational definition, separately by gender in community-dwelling older adults. METHODS: This cross-sectional study recruited respondents via mail. A total of 4798 participants aged ≥65 years participated in the on-site assessment. Social isolation was assessed by "lack of conversation," "lack of passive support," "lack of offering support," and "lack of social participation." Dietary variety was evaluated using the Dietary Variety Score (DVS). RESULTS: The participants' median age was 73 (interquartile range 25-75: 69-77) years, and 2147 (44.7%) were male. After adjusting for covariates, with regard to male participants, a lack of offering support (ß = -0.051, P = 0.019) and a lack of social participation (ß = -0.089, P < 0.001) were associated with a low DVS. For female participants, only a lack of social participation was related to a low DVS (ß = -0.067, P < 0.001). A lack of conversation and passive support were not associated with a low DVS for both genders (P >0.05). CONCLUSION: The results indicate that encouraging social participation, regardless of gender, as well as preventing a lack of offering support for others among men, may contribute to improving individuals' DVS. Geriatr Gerontol Int 2024; ••: ••-••.

Subjective memory concerns and car collisions: A cross-sectional cohort study among older Japanese drivers.

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.

Association of combined low physical activity and low dietary diversity with mild cognitive impairment among community-dwelling Japanese older adults.

Objective: This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults. Methods: Data from 600 older adults (mean age 74.1 ± 6.4 years; 62.0% women) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS) (maximum 30 points) by assessing the one-week consumption frequencies of ten foods. An FFS of ≤ 16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology (NCGG) Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: "Do you engage in moderate levels of physical exercise or sports aimed at health?" and "Do you engage in low levels of physical exercise aimed at health?". Participants who responded "No" to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups. Results: The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio [OR] 2.80, 95% confidence interval [CI] 1.22-6.28). Conclusions: The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

Diversity in productive activities enhances life satisfaction among Japanese community-dwelling older adults: A cross-sectional study.

Few studies have reported an association between diversity in productive activities and life satisfaction; hence, this cross-sectional study conducted in Japan aimed to clarify this association. We assessed the life satisfaction of 4,498 Japanese community-dwelling older adults engaged in productive activities (e.g., paid work, volunteering, taking care of children, and supporting others) using the Life Satisfaction Scale. We took the sum of the number of engaging productive activities as the diversity in productive activities score. A dose-response relationship was observed for each additional productive activity on life satisfaction. Participants who engaged in one, two, three, or four productive activities were more likely to have higher life satisfaction than those who did not engage; the odds ratios (95 % confidence intervals) were 1.19 (1.02-1.39), 1.19 (1.00-1.42), 1.71 (1.37-2.13), and 2.27 (1.58-3.27), respectively. Diversity in productive activities may enhance higher life satisfaction likelihood among Japanese community-dwelling older adults.

Combined effects of loneliness and diabetes mellitus on disability incidence among older Japanese adults.

BACKGROUND: Developed countries worldwide face the challenge of aging populations in which loneliness is problematic, leading to mental and physical health issues. Diabetes mellitus (DM) can cause decreased physical activity, reduced functioning, and depressive symptoms. However, how interactions between loneliness and DM influence health outcomes remains unclear. We aimed to determine the effects of loneliness and DM-related complications on the incidence of disability among older individuals. METHODS: We analyzed data from the Japanese National Center for Geriatrics and Gerontology Study of Geriatric Syndromes for community-dwelling adults aged ≥65 years without initial long-term care needs. Loneliness was assessed using the University of California Los Angeles Loneliness Scale, and DM status was determined based on medical history obtained through face-to-face interviews. Disability incidence was identified by monthly tracking of certifications under the Japanese long-term care insurance system. The combined effect of DM and loneliness on care needs was examined using Cox proportional hazard regression models. RESULTS: Among 5,160 participants, 298 (5.8 %) developed incident disabilities within 24 months. Cox models adjusted for potential confounders revealed a significantly increased disability risk among persons with DM and loneliness. Having DM without loneliness and vice versa were not significant risk factors for disability incidence compared with having neither. CONCLUSIONS: The combination of loneliness with DM was a risk factor for disability development among community-dwelling older adults. Loneliness and DM might be interrelated and associated with disability development, suggesting that support along with assessments of mental health and illness might help to avoid disability in this population.

Artificial intelligence-based morphologic classification and molecular characterization of neuroblastic tumors from digital histopathology.

A deep learning model using attention-based multiple instance learning (aMIL) and self-supervised learning (SSL) was developed to perform pathologic classification of neuroblastic tumors and assess MYCN-amplification status using H&E-stained whole slide digital images. The model demonstrated strong performance in identifying diagnostic category, grade, mitosis-karyorrhexis index (MKI), and MYCN-amplification on an external test dataset. This AI-based approach establishes a valuable tool for automating diagnosis and precise classification of neuroblastoma tumors.

A Perspective on the CD47-SIRPA Axis in High-Risk Neuroblastoma.

Neuroblastoma is a pediatric cancer with significant clinical heterogeneity. Despite extensive efforts, it is still difficult to cure children with high-risk neuroblastoma. Immunotherapy is a promising approach to treat children with this devastating disease. We have previously reported that macrophages are important effector cells in high-risk neuroblastoma. In this perspective article, we discuss the potential function of the macrophage inhibitory receptor SIRPA in the homeostasis of tumor-associated macrophages in high-risk neuroblastoma. The ligand of SIRPA is CD47, known as a "don't eat me" signal, which is highly expressed on cancer cells compared to normal cells. CD47 is expressed on both tumor and stroma cells, whereas SIRPA expression is restricted to macrophages in high-risk neuroblastoma tissues. Notably, high SIRPA expression is associated with better disease outcome. According to the current paradigm, the interaction between CD47 on tumor cells and SIRPA on macrophages leads to the inhibition of tumor phagocytosis. However, data from recent clinical trials have called into question the use of anti-CD47 antibodies for the treatment of adult and pediatric cancers. The restricted expression of SIRPA on macrophages in many tissues argues for targeting SIRPA on macrophages rather than CD47 in CD47/SIRPA blockade therapy. Based on the data available to date, we propose that disruption of the CD47-SIRPA interaction by anti-CD47 antibody would shift the macrophage polarization status from M1 to M2, which is inferred from the 1998 study by Timms et al. In contrast, the anti-SIRPA F(ab')2 lacking Fc binds to SIRPA on the macrophage, mimics the CD47-SIRPA interaction, and thus maintains M1 polarization. Anti-SIRPA F(ab')2 also prevents the binding of CD47 to SIRPA, thereby blocking the "don't eat me" signal. The addition of tumor-opsonizing and macrophage-activating antibodies is expected to enhance active tumor phagocytosis.