Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial.

AIMS: Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia. METHODS: This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance. RESULTS: In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively. CONCLUSIONS: XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.

Japan-Multimodal Intervention Trial for the Prevention of Dementia: A randomized controlled trial.

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.

Association between oral frailty and sarcopenia among frailty clinic outpatients: A cross-sectional study.

OBJECTIVES: In this study, we aimed to investigate the prevalence of oral frailty and explore its relationship with oral function and sarcopenia among older outpatients. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively included older patients who visited a frailty outpatient clinic. We assessed total oral frailty employing, among other measures, oral diadochokinesis (/ta/ sound) for tongue-lip movement and tongue pressure. Patients who did not meet the cut-off values for three or more of these were classified as having oral frailty. Sarcopenia was assessed according to Asian Working Group for Sarcopenia 2019 criteria and analyzed for the relationship with oral function. RESULTS: The mean ± standard deviation age of the 111 patients was 77.2 ± 5.7 y; 63 were women (57%). Fifteen patients (14%) had either sarcopenia or dynapenia. The overall prevalence of oral frailty was 38%, with no significant difference in its prevalence between the sarcopenia/dynapenia group (44%) and the robust (no sarcopenia/dynapenia) group (35%). The following oral function assessments significantly differed between the sarcopenia/dynapenia group and the robust group: median (interquartile range) total oral frailty score, 2 (2-4) and 2 (1-3) (P = 0.019); tongue-lip motor function, 5.4 ± 1.2 and 5.9 ± 1.2 times/s (P = 0.049); and tongue pressure, 27.3 ± 8.5 kPa and 31.7 ± 8.0 kPa (P = 0.009). CONCLUSIONS: Approximately 40% of patients exhibited a decline in oral function regardless of the presence of sarcopenia. Sarcopenia and dynapenia may particularly affect tongue function. Although assessing patients for sarcopenia is crucial, separate evaluations of oral function should also be considered.

[A framework for promoting and evaluating "Kayoi-no-ba" initiatives according to the Plan-Do-Check-Action cycle: The ACT-RECIPE framework].

Objective　In 2019, the Ministry of Health, Labour and Welfare emphasized the importance of promoting "Kayoi-no-ba" (or "places to go") initiatives according to the Plan-Do-Check-Action (PDCA) cycle. However, it proposed no specific promotion measures or standardized evaluation frameworks. This study is intended to propose a framework for local government officials to promote and evaluate "Kayoi-no-ba" initiatives according to the PDCA cycle.Methods　The working group (WG) conducted a narrative review of research and extracted evaluation models and indicators that could be used to create the framework. The co-researcher review committee discussed a draft framework prepared by the WG, and the WG revised it based on the discussion; this process was repeated four times. Using the completed framework, we calculated the score of the "Kayoi-no-ba" initiatives in 50 Tokyo municipalities and conducted regional correlation analyses on the relationship between the score of the "Kayoi-no-ba" initiatives in 50 Tokyo municipalities and the number of "Kayoi-no-ba" per 1,000 older persons.Results　The completed framework (named "ACT-RECIPE" by rearranging the underlined characters below) comprised the following six evaluation phases: (1) Comprehension: understanding the key lessons around disability and frailty prevention, and the necessity for "Kayoi-no-ba"; (2) Research and Planning: clarifying the current status of "Kayoi-no-ba," the strengths of the community, and the issues to be addressed through a community assessment, and developing a plan to resolve the issues; (3) Team Building and Collaboration: building a team by collaborating with organizations to solve problems; (4) Implementation: implementing the initiatives necessary to solve problems; (5) Evaluation: verifying changes in output and outcome indicators from the initiatives; and (6) Adjustment and Improvement: re-examining plans, teams, content, and goals based on the evaluation results. In these six phases, we designated 10 core items and accompanying subitems. The median score rate of the ACT-RECIPE framework in 50 municipalities was 75% for "Comprehension," 61% for "Research and Planning," 69% for "Team Building and Collaboration," 64% for "Implementation," 31% for "Evaluation," and 56% for "Adjustment and Improvement," and the mean ACT-RECIPE score rate was 57%. A significant positive correlation (rs=0.43, P=0.002) was observed between the ACT-RECIPE mean score rate and the number of "Kayoi-no-ba" per 1,000 older persons.Conclusion　We proposed the ACT-RECIPE as a framework for promoting and evaluating "Kayoi-no-ba" initiatives according to the PDCA cycle. We hope that this framework will lead to further progress in "Kayoi-no-ba" initiatives and facilitate evaluation of their effectiveness according to the PDCA cycle.

Aging populations and perspectives of geriatric medicine in Japan.

It is well known that Japan's population is aging, and the number of people older than 75 years is increasing significantly. Since older people, especially old individuals, are often multimorbid and cannot be always successfully treated and cared for by individual organ-specific treatment, it is essential to utilize knowledge of geriatrics when treating such older patients. Therefore, it is indisputable that education on geriatric medicine is extremely important in Japan, which is the country with the largest aging population. However, the number of universities in Japan that offer geriatrics courses is decreasing. This means that many medical students become doctors without learning the essential characteristics of medical care for older patients despite the need for prompt treatment of older patients in clinical practice in Japan, which is a major obstacle to the development of geriatric medicine in Japan. Here, we review the current status of geriatrics in Japan and overseas and consider the future of geriatrics education to provide holistic and cost-effective medical care for older patients and improve their quality of life and well-being.

Association between intrinsic capacity and oral health in older patients in a frailty clinic.

PURPOSE: This study aimed to investigate how intrinsic capacity (IC) deficit is associated with oral functional decline. METHODS: This cross-sectional study enrolled older adults at a research hospital frailty clinic between July 2021 and May 2023. IC evaluation included the locomotion, cognition, vitality, psychology, and sensory domains. Criteria for deficits were established within each domain, and the number of IC deficit domains was calculated for each patient. Oral function assessment included oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function. Patients who met three or more criteria were classified into the oral hypofunction (OHF) group. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between IC deficit and OHF. RESULTS: Of 222 included patients (mean age 78.3 ± 6.3 years; 39.6% men), 105 (47.3%) met the criteria for OHF. This OHF group showed a significantly higher prevalence of locomotion, cognition, psychology, and sensory domain deficits than the normal oral function group. Multivariate analysis adjusted for age and sex revealed a significant association between IC deficits and OHF (odds ratio [OR], 1.33; 95% confidence interval [CI] 1.04-1.70). A significant association was also observed between the locomotion domain and OHF (OR, 2.06; 95% CI 1.13-3.76). CONCLUSION: This study highlights the potential relationship between the number of IC domain deficits and oral functional decline, with the most significant domain being locomotion. Furthermore, it suggests a possible link between sensory and oral function.

Fragility Fracture Network-Japan: The challenge of establishment of a national hip fracture database and successful achievement of nationwide health system change for hip fracture care in Japan.

BACKGROUND: In April 2022, a new reimbursement scheme for hip fracture was implemented by the Japanese health ministry. Japan is one of the world's most aged societies, facing a significant, rapidly growing burden of osteoporosis and fragility fractures. The incidence of hip fractures is projected to increase from 240,000 in 2020 to 320,000 by 2040. In 2015, Fragility Fracture Network-Japan (FFN-Japan) was formally established as a nonprofit organization in order to create the optimal fragility fracture care system in Japan. METHODS: FFN-Japan launched the Japan National Hip Fracture Database (JNHFD) in 2017, initially with only eight participating hospitals across Japan. The number of patients enrolled from May 2017 to the end of 2020 in the JNHFD from the 16 hospitals registered the patients during this period with amounting to 4271 patients in total. FFN-Japan invited officials from the Ministry of Health, Labor and Welfare (MHLW) to participate in round table meetings to discuss the data collected in the JNHFD and to consider opportunities for nationwide improvement in hip fracture care. RESULTS: The proportion of patients who underwent surgery within 36 h of arrival at hospital was 48.1% in 2018, 58.6% in 2019, and 44.9% in 2020 indicating the delay of surgery. Regarding secondary fracture prevention, initiation of osteoporosis treatment during the in-patients was 60.2% in 2018, 54.0% in 2019, and 64.5% in 2020 indicating the inadequate post fracture care. In April 2022, the Central Social Insurance Medical Council of the Japanese MHLW announced a new reimbursement scheme for hip fracture care including two key components: Early surgery (within 48 h from injury) and Secondary fracture prevention immediately after fracture. DISCUSSION: The new reimbursement scheme of hip fracture care in Japan will catalyze and underpin major improvements on acute multidisciplinary care and post-fracture care with secondary fracture prevention. FFN-Japan played a key role on these policy changes to the health system by means the close collaboration and ongoing communication with the government. CONCLUSION: Within five years of establishment of the JNHFD, FFN-Japan in collaboration with visionary leaders from the Japanese government have successfully achieved a major reform of the Japanese health system's reimbursement of hip fracture care. This reform has laid the foundation for transformation of management of this debilitating and life-threatening injury that currently afflicts almost a quarter of a million older Japanese citizens each year.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

Behavioral and psychological symptoms of dementia and mortality risk among people with cognitive impairment: an 8-year longitudinal study from the NCGG-STORIES.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia from the early stages and can appear even in mild cognitive impairment (MCI). However, the prognostic impact of BPSD is unclear. This study examined the association between BPSD and mortality among people with cognitive impairment. METHODS: This longitudinal study involved 1,065 males and 1,681 females (mean age: males = 77.1 years; females = 78.6 years) with MCI or dementia diagnosis, from the National Center for Geriatrics and Gerontology-Life Stories of People with Dementia (NCGG-STORIES), a single-center memory clinic-based cohort study in Japan that registered first-time outpatients from 2010-2018. Information about death was collected through a mail survey returned by participants or their close relatives, with an up to 8-year follow-up. BPSD was assessed using the Dementia Behavior Disturbance Scale (DBD) at baseline. RESULTS: During the follow-up period, 229 (28.1%) male and 254 (15.1%) female deaths occurred. Cox proportional hazards regression analysis showed that higher DBD scores were significantly associated with increased mortality risk among males, but not females (compared with the lowest quartile score group, hazard ratios [95% confidence intervals] for the highest quartile score group = 1.59 [1.11-2.29] for males and 1.06 [0.66-1.70] for females). Among the DBD items, lack of interest in daily living, excessive daytime sleep, and refusal to receive care had a higher mortality risk. CONCLUSIONS: The findings suggest a potential association between BPSD and poor prognosis among males with cognitive impairment.

Elevated Risk of Dementia Diagnosis in Older Adults with Low Frequencies and Durations of Social Conversation.

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.

Longitudinal association between muscle and bone loss: Results of US and Japanese cohort studies.

BACKGROUND: Muscle and bone are physiologically interconnected, but joint changes of muscle and bone with aging, and whether the muscle-bone changes are different by sex and by country has been little studied. We examined longitudinal associations of bone mineral density (BMD) and muscle mass or muscle strength in community-dwelling 65 years or older in the United States and Japan. METHODS: The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5 ± 7.5 years; women, 49.8%) and 1998 women and men from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) (mean age, 70.0 ± 4.5 years; women, 51.4%). Median follow-up was 4.6 (min-max, 0-15.4) years in the BLSA and 4.0 (min-max, 0-13.4) years in the NILS-LSA. We selected visits at which participants had BMD (whole body, pelvic, femoral neck, trochanter, and Ward's triangle BMDs) and muscle mass [appendicular lean mass, (ALM)] measured by DXA scan. In each bone site, we ran cohort-specific bivariate linear mixed-effects models adjusted for baseline age, sex, body height, body weight, fat mass, education year, and smoking status. Race was an additional adjustment in the BLSA. Additionally, we performed sex-specific analyses. RESULTS: In the BLSA, the rate of change in ALM positively correlated with the rate of change in the whole body (rho = 0.30, P < 0.0001) and pelvic BMD (rho = 0.24, P < 0.0001), but not in trochanter, femoral neck, or Ward's triangle BMD (P > 0.05). In the NILS-LSA, ALM positively correlated with the rate of change in all bone sites (rho ranged from 0.20 to 0.71, P < 0.01). In women, ALM positively correlated with the rate of change in all bone sites in both cohorts (in the NILS-LSA, rho ranged from 0.35 to 0.91, P < 0.01; in the BLSA, rho ranged from 0.26 to 0.56, P < 0.05) except for femoral neck BMD in the BLSA. In men, ALM positively correlated with pelvic, trochanter, and Ward's triangle BMD in the NILS-LSA (rho ranged from 0.45 to 0.68, P < 0.0001), and whole body and trochanter BMD in the BLSA (both, rho = 0.20, P < 0.05). CONCLUSIONS: Muscle loss co-occurred with bone loss in both cohorts, but the association in the NILS-LSA tended to be stronger than in the BLSA, and the association was higher in women than in men, implying that the association may differ by sex and country.

Develop and Validate a Prognostic Index With Laboratory Tests to Predict Mortality in Middle-Aged and Older Adults Using Machine Learning Models: A Prospective Cohort Study.

BACKGROUND: Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals. METHODS: We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan. RESULTS: Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778-0.819) and 0.756 (95% CI: 0.694-0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790-0.811) and 0.809 (95% CI: 0.774-0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose-response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results. CONCLUSIONS: The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making.

Prevalence of oral frailty and its association with dietary variety, social engagement, and physical frailty: Results from the Oral Frailty 5-Item Checklist.

AIM: This cross-sectional study had two aims: to assess the prevalence of oral frailty (OF), according to the Oral Frailty 5-Item Checklist (OF-5), among community-dwelling older adults; and to examine the associations among oral frailty, dietary variety, social engagement, and physical frailty. METHODS: We pooled data from two population-based studies (the Otassha Study and the Itabashi Longitudinal Study on Aging). With the OF-5, OF is characterized by the presence of two or more of the following: (i) fewer teeth, (ii) difficulty in chewing, (iii) difficulty in swallowing, (iv) dry mouth, and (v) low articulatory oral motor skills. We calculated the OF prevalence for each sex. We assessed dietary variety, social engagement, and physical frailty. Generalized structural equation modeling was employed to investigate the associations among oral frailty, low dietary variety (dietary variety score ≤3), social isolation (Lubben Social Network Scale score <12), and physical frailty (Japanese version of the Cardiovascular Health Study score ≥3). RESULTS: A total of 1206 individuals (626 women and 580 men) with a mean age of 74.7 years were included. The prevalence of OF was 36.7%, and it increased with age; however, there was no significant sex difference. OF was significantly indirectly associated with physical frailty via low dietary variety (odds ratio, 1.43; 95% confidence interval, 1.04-1.97) and social isolation (odds ratio, 1.42; 95% confidence interval, 1.04-1.94). CONCLUSIONS: Two of five community-dwelling older adults exhibited OF. Low dietary variety and social isolation are potential underlying mechanisms through which OF is indirectly associated with physical frailty. Geriatr Gerontol Int 2024; 24: 371-377.

The burden of frailty in heart failure: Prevalence, impacts on clinical outcomes and the role of heart failure medications.

BACKGROUND: Frailty often coexists with heart failure (HF), which significantly aggravates the clinical outcomes of older adults. However, studies investigating the interplay between frailty and HF in older adults are scarce. We aimed to assess the prevalence of frailty using the cumulative deficit approach and evaluate the impacts of frailty on health utilization, use of HF-related medications and adverse clinical outcomes (all-cause mortality, all-cause readmissions and HF readmissions) among older HF patients. METHODS: A total of 38 843 newly admitted HF patients were identified from Taiwan's National Health Insurance Research Database and categorized into three frailty subgroups (fit, mild frailty and severe frailty) based on the multimorbidity frailty index. Cox regression models and Fine and Gray subdistribution hazard models were used to estimate the impacts of frailty on clinical outcomes at 1 and 2 years of follow-up. Generalized estimating equation models were further conducted to evaluate the associations between longitudinal and time-varying use of HF-related medications and clinical outcomes among distinct frailty subgroups. RESULTS: Of 38 843 older HF patients (mean age 80.4 ± 8.5 years, 52.3% females) identified, 68.3% were categorized as frail (47.5% of mild frailty and 20.8% of severe frailty). The median number of readmissions (fit: 1 [inter-quartile range-IQR 2], mild frailty: 1 [IQR 2] and severe frailty: 2 [IQR 3]) increased with the severity of frailty. Only 27.3% of HF patients died of cardiovascular diseases regardless of their frailty status. Compared with the fit group, the severe frailty group was associated with increased risk of all-cause mortality (adjusted hazard ratio 1.16, 95% confidence interval [CI] 1.11-1.21), all-cause readmissions (subdistributional hazard ratio (sHR) 1.21, 95% CI 1.16-1.25) and HF-related readmissions (sHR 1.14, 95% CI 1.09-1.20) at 2 years of follow-up. Those who used triple or more HF-related medications were at lower risk for all-cause readmissions (adjusted odds ratio [aOR] 0.49, 95% CI 0.44-0.54) and HF-related readmissions (aOR 0.42, 95% CI 0.37-0.47) at 2 years of follow-up even in the severe frailty group. CONCLUSIONS: Frailty is highly prevalent and associated with increased risk of all-cause mortality, all-cause readmissions and HF readmissions among older HF patients. Those who were using triple or more HF-related medications were at lower risk of adverse clinical outcomes across distinct frailty subgroups. Further studies are needed to optimize the treatment strategies for older HF patients with distinct frailty status.

Higher Cholesterol Absorption Marker at Baseline Predicts Fewer Cardiovascular Events in Elderly Patients Receiving Hypercholesterolemia Treatment: The KEEP Study.

BACKGROUND: Higher cholesterol absorption has been reported to be related to a higher incidence of cardiovascular events (CVEs). The KEEP (Kyushu Elderly Ezetimibe Phytosterol) study, a substudy of the EWTOPIA 75 (Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older) study, investigated the relationships of cholesterol absorption and synthesis markers with CVEs in older old individuals with hypercholesterolemia, particularly in relation to ezetimibe treatment. METHODS AND RESULTS: Eligible patients were those aged ≥75 years who had low-density lipoprotein cholesterol ≥140 mg/dL, no history of coronary artery disease, and no recent use of lipid-lowering drugs. Participants were randomly assigned into a diet-only or diet-plus-ezetimibe group. Baseline and 24-week follow-up blood samples were analyzed for cholesterol absorption (eg, campesterol) and synthesis markers (eg, lathosterol). Of 1287 patients, 1061 patients with baseline measurement were analyzed. Over a median follow-up of 4.0 years, 64 CVEs occurred. Higher campesterol levels at baseline were significantly associated with a lower risk of CVEs. After adjustment for sex, age, and treatment, the hazard ratios for the lowest to highest quartile categories of baseline campesterol were 1.00 (reference), 0.59 (95% CI, 0.30-1.17), 0.44 (95% CI, 0.21-0.94), and 0.44 (95% CI, 0.21-0.93), respectively (trend P=0.01). This association persisted after further adjustment for hypertension, diabetes, and other cardiovascular risk factors. Neither interactions with ezetimibe treatment nor mediating effects of the changes in cholesterol absorption markers were observed. CONCLUSIONS: The KEEP study indicated that higher campesterol levels without lipid-lowering drugs were associated with a lower incidence of CVEs in older old individuals with hypercholesterolemia who were subsequently treated with diet or ezetimibe. REGISTRATION: URL: https://www.umin.ac.jp; unique identifier: UMIN000017769.

Relationship between mortality and vitality in patients with mild cognitive impairment/dementia: An 8-year retrospective study.

AIM: The study aimed to investigate the association of vitality, as measured using the vitality index (Vix), with the survival outcomes of older adults with mild cognitive impairment (MCI) or dementia. METHODS: We analyzed data from 3731 patients in the National Center for Geriatrics and Gerontology - Life Stories of Individuals with Dementia cohort from July 2010 to September 2018. The main focus was to correlate Vix scores with the time from the initial visit to death. Vix was categorized into "moderately to severely impaired" (0-7 points), "mildly impaired" (8-9 points), and "normal" (10 points) groups. Survival outcomes were assessed using a Cox proportional hazards model, adjusted for various factors. We conducted a mediation analysis to evaluate the effect of body mass index (BMI), instrumental activities of daily living (IADL), and basic activities of daily living (BADL) on the association between vitality and mortality. Stratified analysis was also conducted for the Mini-Mental State Examination groups. RESULTS: We included 2740 patients with an average follow-up of 1315 days. The mortality rate was 15.7%. The Vix distribution was 16% at 0-7 points; 40%, 8-9 points; and 44%, 10 points. Patients in the "moderately to severely impaired" category, characterized by lower Vix scores, exhibited notably higher mortality rates. Mediation effects emphasized the significant roles of BMI, IADL, and BADL in influencing survival outcomes. CONCLUSIONS: Vitality significantly influences patient survival rates. The association between vitality and mortality seems to be mediated by IADL and BADL, which has significant clinical implications. Geriatr Gerontol Int 2024; 24: 221-228.

Dyadic Art Appreciation and Self-Expression Program (NCGG-ART) for People with Dementia or Mild Cognitive Impairment and Their Family Caregivers: A Feasibility Study.

BACKGROUND: Non-pharmacological interventions effective for depressive mood and bilateral relationships among persons with cognitive impairment (PwCI) and their family caregivers (FCGs) have not been established. OBJECTIVE: To examine the feasibility of a newly developed group-based art appreciation and self-expression program (NCGG-ART) for dyads of PwCI and their FCGs. METHODS: This pilot randomized control trial included 34 dyads of PwCI diagnosed with mild to moderate Alzheimer's disease or mild cognitive impairment, and their FCGs, from an outpatient rehabilitation service (Holistic Physio-Cognitive Rehabilitation [HPCR]). Participants were randomly divided equally into the HPCR (control group) or NCGG-ART and HPCR (intervention group) groups. Both included 1-hour weekly, 6-week programs. The primary outcome was depressive symptoms among FCGs assessed using the Patient Health Questionnaire-9 (PHQ-9). Feasibility outcomes included participant satisfaction and motivation. FCGs were interviewed about their experiences and feelings regarding the program, which were analyzed using content analysis. RESULTS: Thirty-two dyads (intervention group:16; control group:16) completed the study period. High participation rates, satisfaction, and motivation were demonstrated throughout the intervention. Scores in the PHQ-9 among FCGs did not show positive effects: mean changes in the score were 1.3 for the intervention group and -0.8 for the control group (Cohen d:0.56). However, the qualitative analysis revealed favorable experiences and feelings of the FCGs, such as positive emotions, social interactions, and person-centered attitudes to and positive relationships with PwCI. CONCLUSIONS: This program demonstrated high feasibility with FCGs' favorable responses to emotions and relationships with PwCI, ensuring future investigations with a confirmatory study design.

Combined impact of physical frailty and social isolation on use of long-term care insurance in Japan: A longitudinal observational study.

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.

Implication of grip strength assessment for the management of body weight in disability prevention in older adults.

BACKGROUND: Although body mass index (BMI) and grip strength (GS) are both predictors of disability, their joint effect on predicting incident disability remains uncertain. We examined whether the effect of BMI on incident disability can be modulated by GS in community-dwelling older people in Japan. METHODS: A total of 1486 community-dwellers in Japan (731 men and 755 women, aged 65-82 years) who participated in the 2nd to 7th waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project, were followed up to 20 years. Twelve subgroups were created according to the intersections of GS (sex-specific tertiles: low, intermediate, and high) and BMI (underweight 1, <18.5; underweight 2, 18.5-<21.5; normal, 21.5-<25.0; and overweight/obese, ≥25.0 kg/m2 ). Incident disability was defined as requiring care need level 1 or higher, as per the long-term care insurance system in Japan. The hazard ratios (HR) and corresponding 95% confidence intervals (CI) of incident disability (the 'high GS-normal BMI' subgroup was used as the reference) were calculated using a multivariable-adjusted Cox proportional hazards model. The model was adjusted for baseline characteristics on sex, participation wave, smoking, depressive symptoms, total physical activity, disease history, education level, residential status, and energy intake. RESULTS: Compared with that for participants in the 'high GS-normal BMI' group, the risk of incident disability was higher for participants in the 'low GS-normal BMI', 'low GS-overweight/obese', 'intermediate GS-underweight 1' and 'intermediate GS-overweight/obese' groups. The multivariable-adjusted HR (95% CI) were 1.72 (1.27-2.32, P value<0.001), 1.81 (1.27-2.58, P value = 0.001), 2.42 (1.35-4.32, P value = 0.003) and 1.53 (1.06-2.20, P value = 0.023), respectively. The results did not change substantially when participants with disability occurring within 1 and 2 years of follow-up were excluded, or when the competing events were death without incident disability or dementia. CONCLUSIONS: The joint effect of BMI and GS was more pronounced in those of normal weight or overweight/obese status and low GS, along with underweight or overweight/obese status and intermediate GS in predicting disability. The lack of observed joint effect for those underweight with low GS was likely due to insufficient sample size. GS consideration is necessary for weight management in older adults, and interventions for individuals who are underweight or overweight/obese with adequate GS need not be prioritized for disability prevention.