Enzyme structure correlates with variant effect predictability.

Protein engineering increasingly relies on machine learning models to computationally pre-screen promising novel candidates. Although machine learning approaches have proven effective, their performance on prospective screening data leaves room for improvement; prediction accuracy can vary greatly from one protein variant to the next. So far, it is unclear what characterizes variants that are associated with large prediction error. In order to establish whether structural characteristics influence predictability, we created a novel high-order combinatorial dataset for an enzyme spanning 3,706 variants, that can be partitioned into subsets of variants with mutations at positions exclusively belonging to a particular structural class. By training four different supervised variant effect prediction (VEP) models on structurally partitioned subsets of our data, we found that predictability strongly depended on all four structural characteristics we tested; buriedness, number of contact residues, proximity to the active site and presence of secondary structure elements. These dependencies were also found in several single mutation enzyme variant datasets, albeit with dataset specific directions. Most importantly, we found that these dependencies were similar for all four models we tested, indicating that there are specific structure and function determinants that are insufficiently accounted for by current machine learning algorithms. Overall, our findings suggest that improvements can be made to VEP models by exploring new inductive biases and by leveraging different data modalities of protein variants, and that stratified dataset design can highlight areas of improvement for machine learning guided protein engineering.

Association of open skill exercise and long-chain polyunsaturated fatty acid intake with brain volume changes among older community-dwelling Japanese individuals.

Considering that a multifactorial lifestyle approach may prove more effective than a single factor approach to improve or maintain brain health, we evaluated the association of exercise (open skill exercise [OSE] or closed skill exercise [CSE]) combined with long-chain polyunsaturated fatty acid (LCPUFAs) (docosahexaenoic acid [C22:6n-3, DHA], eicosapentaenoic acid [C20:5n-3, EPA], and arachidonic acid [C20:4n-6, ARA]) intake with brain atrophy among older Japanese individuals (n = 795, aged 60-88 years) without a self-reported history of dementia based on the datasets of a two-year longitudinal study. Brain volumes were measured using three-dimensional T1-weighted brain magnetic resonance imaging for follow-up periods of two years. The associations between multivariate-adjusted changes in brain volumes and OSE or CSE frequency (≥ once/month and < once/month) along with LCPUFA intake (≥ median and < median) at the baseline were assessed using a general linear model. Subgroup analysis was performed by restricting DHA and EPA intakes (n = 263; median, 323 mg/d), which represented levels similar to those in countries with low fish consumption. Higher OSE frequencies, ARA intakes, and their combination were inversely associated with decreases in total gray matter and frontal cortex volumes. In subgroup analysis, a combination of higher OSE frequencies and DHA intakes was also associated with a smaller decrease in total gray matter volume. Overall, our findings suggest that regular OSE engagement and appropriate LCPUFA intake may contribute to preventing brain volume decreases in older individuals.

Association between a combination of cognitively stimulating leisure activities and long-chain polyunsaturated fatty acid intake on cognitive decline among community-dwelling older Japanese individuals.

Multifactorial lifestyle approaches could be more effective than a single factor for maintaining cognitive function. This study investigated the association of combining cognitively stimulating leisure activities (CSLAs), including puzzles, quizzes, and cognitive training games, with intake of long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), on cognitive function in the older Japanese individuals without dementia. Participants were community-dwelling Japanese individuals without a self-reported history of dementia (n = 906, aged 60-88 years) from datasets of a 2-year longitudinal study (baseline: 2006-2008 and follow-up: 2008-2010). CSLA engagement and LCPUFA intake were divided into high and low groups according to frequency (≥once/week and

Low Serum Total Carotenoids and ß-Cryptoxanthin Are Associated with Low Lean Body Mass in Older Community-Dwellers in the National Institute for Longevity Sciences-Longitudinal Study of Aging: A 4-Y Longitudinal Study.

BACKGROUND: Although diets rich in carotenoids are associated with muscle health and a reduced risk of disability, the relationship between carotenoids and low lean body mass has not been fully elucidated. OBJECTIVES: This study aimed to clarify the relationship between serum carotenoid concentrations and low lean body mass over 4 y in older Japanese community-dwellers. METHODS: A total of 750 adults aged ≥60 y participated in the National Institute for Longevity Sciences-Longitudinal Study of Aging. Individuals with a low lean body mass and muscle strength or gait speed at baseline were excluded. Baseline serum α-carotene, ß-carotene, ß-cryptoxanthin, zeaxanthin, lutein, and lycopene were measured. Low lean body mass was defined as appendicular lean mass relative to the measured height (ALM/ht2) of <7.0 kg/m2 in males and <5.4 kg/m2 in females, according to the criteria of the Asian Working Group for Sarcopenia 2019. A generalized estimating equation was used to estimate the odds ratio and 95% confidence interval for low lean body mass according to tertiles of total and individual carotenoids at baseline, adjusted for sex, age, season, follow-up months, education years, economic status, current smoking status, a history of ischemic heart disease, stroke, hypertension, dyslipidemia, diabetes mellitus, and metabolic equivalents. RESULTS: Low serum total carotenoids were associated with low ALM/ht2, and the odds ratios of low ALM/ht2 in the third tertile of total carotenoids were significantly lower than those in the first tertile after adjusting for covariates. The odds ratios of low ALM/ht2 in the third tertile of ß-cryptoxanthin were significantly associated with those in the first tertile after adjusting for covariates (P = 0.03); however, no trend was observed for this relationship. CONCLUSIONS: These findings indicate that low serum total carotenoids and serum ß-cryptoxanthin are associated with low lean body mass in older Japanese community-dwellers.

The relationship between the dietary index based Meiji nutritional profiling system for adults and lifestyle-related diseases: a predictive validity study from the National Institute for Longevity Sciences-Longitudinal Study of Aging.

Background: Nutritional profiling system (NPS) holds promise as a public health tool for companies to measure product healthiness and for individuals in making healthier food choices. The Meiji NPS for adults specifically targets lifestyle-related diseases prevalent among Japan's adult population, including overweight/obesity, hypertension, diabetes, and dyslipidemia. This study examined the cross-sectional association between the Meiji NPS for adults Dietary Index (MNfA-DI) and indicators of lifestyle-related diseases in a population. Methods: The study comprised 1,272 middle-aged individuals (40-64 years, 50.1% male) who participated in the seventh wave (2010-2012) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project, with no missing data on three-day dietary records. The MNfA-DI was computed at the individual diet level (accounting for the whole diet) using arithmetic energy-weighted means. A higher MNfA-DI indicated a greater nutritional quality of an individual's overall diet. Lifestyle-related disease indicators included body mass index (BMI, kg/m2), body fat (%), systolic and diastolic blood pressure (mmHg), fasting plasma glucose (mg/dL), HbA1c (%), triglyceride levels (mg/dL), LDL, and HDL cholesterol levels (mg/dL). A multiple regression model was used to assess the association between the MNfA-DI and lifestyle-related disease indicators, adjusting for demographics, socioeconomic status, lifestyle factors, disease history, and energy intake as covariates, depending on the outcome. Results: The median (interquartile range) age and MNfA-DI were 53.0 (46.0, 59.0) years and 10.1 (6.0, 14.0) points, respectively. MNfA-DI was negatively associated with body fat [partial regression coefficient (95% confidence interval) -0.04 (-0.07, -0.01)], diastolic blood pressure [-0.08 (-0.17, -0.002)], fasting plasma glucose [-0.18 (-0.33, -0.01)], and triglyceride [-1.36 (-2.16, -0.55)]. Additionally, MNfA-DI was also associated with almost indicators (except for LDL and HDL cholesterol) among participants with a BMI between 18.5 and 24.9 kg/m2. Conclusion: These findings suggest that the Meiji NPS for adults could be associated with a lower risk of lifestyle-related diseases. In addition, from a public health nutrition perspective, the Meiji NPS for adults may be useful to assess the food healthiness of the adult population.

Association between milk consumption in middle age and frailty in later life: The Aichi Workers' cohort study.

AIM: Several studies have shown that dairy consumption in old age is effective in preventing frailty. However, there is a lack of evidence regarding the association between milk consumption during middle age and the development of frailty in old age. Therefore, we carried out an investigation to explore the association between milk consumption during middle age and development of frailty examined after over 15 years of follow up in a long-term cohort study in Japan. METHODS: We studied 265 participants aged 60-79 years (212 men and 53 women) in 2018, who participated in both the baseline survey in 2002 and the frailty assessment in 2018. The amount of milk consumption (g/day) at baseline was age- and energy-adjusted, and classified into three categories (no, low and high consumption: 0 g/day, ≤135.86 g/day, >135.86 g/day in men and 0 g/day, ≤126.44 g/day, >126.44 g/day in women). Odds ratios (OR) and 95% confidence intervals (CI) for prefrailty/frailty after adjusting for lifestyles at baseline, stratified by sex, were estimated using logistic regression analysis. RESULTS: The prevalence of prefrailty/frailty in 2018 was 37.7% and 28.3% in men and women, respectively. Milk consumption categories were inversely associated with the prevalence of prefrailty/frailty in men (OR 0.34, 95% CI 0.14-0.84 in low consumption; OR 0.31, 95% CI 0.10-0.95 in high consumption; P < 0.05), but not in women (OR 0.53, 95% CI 0.11-2.65; P = 0.44). CONCLUSIONS: In this study, milk intake in middle-aged men was inversely associated with the prevalence of prefrailty/frailty later in life. Geriatr Gerontol Int 2024; 24: 700-705.

Associations between information and communication technology use and frailty in community-dwelling old-old adults: results from the ILSA-J.

OBJECTIVES: Frailty is a significant cause of adverse health events including long-term care and hospitalization. Although information and communication technology (ICT) has become an integral part of modern life, it remains unclear whether ICT use is associated with frailty. DESIGN: A cross-sectional study (Integrated Longitudinal Studies on Aging in Japan, ILSA-J). SETTING AND PARTICIPANTS: Aged 75 and older data from the ILSA-J in 2017 (n = 2893). METHODS: ICT use was measured using the technology usage sub-items of the Japan Science and Technology Agency Index of Competence. Specifically, the use of mobile phones, ATMs, DVD players, and sending e-mails were rated as "yes" (able to do) or "no" (unable to do), with the first quintile (≤1 point) defined as ICT non-users. Frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria based on the phenotype model (e.g., weight loss, slowness, weakness, exhaustion, and low activity). Further, multivariate logistic regression analysis analyzed its association with ICT use. Subgroup analyses were stratified according to gender, years of education, and living arrangements. RESULTS: Higher ICT use was not associated with frailty after adjusting for covariates (odds ratio [OR]: 0.53; 95%CI 0.39-0.73). Similar associations were found in the sub-groups of women (OR 0.45, 95%CI 0.30-0.66), <13 years of education (OR 0.48, 95%CI 0.34-0.67), living alone (OR 0.46, 95%CI 0.27-0.79), and living together (OR 0.57, 95%CI 0.38-0.85). No association existed between using ICT and frailty in the sub-groups of men and ≥13 years of education. CONCLUSIONS AND IMPLICATIONS: Higher ICT use is associated with the absence of frailty in individuals 75 years and older. Such benefits may be particularly pronounced in women, those with lower levels of education, and older adults living alone or with others.

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 of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study.

Introduction: Taurine has diverse valuable biological functions, including antioxidant activity and regulation of osmotic pressure. Maintaining physical fitness from middle age is important for healthy life expectancy. Although taurine administration improves muscle endurance and strength, its role in maintenance remains unclear. We aimed to clarify the longitudinal taurine intake association with fitness changes. Methods: Participants comprised men and women aged ≥40 years who participated in the third (2002-2004; Baseline) and seventh (2010-2012; Follow-up) waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) and completed a 3-day dietary weights recording survey at baseline. A table of taurine content was prepared for 751 foods (including five food groups: Seaweed; Fish and shellfish; Meat; Eggs; and Milk and dairy products) from the Standard Tables of Food Composition in Japan (1,878 foods) 2010. Four physical fitness items (knee extension muscle strength, sit-and-reach, one-leg standing with eyes closed, and maximum walking speed) were measured at baseline and follow-up. We analyzed the association of taurine intake with physical fitness change, employing a general linear model (GLM) and trend tests for baseline taurine intake and follow-up fitness change. Adjustments included baseline variables: sex, age, height, weight, educational level, self-rated health, smoking status, depressive symptoms, and clinical history. Results: The estimated average daily taurine intake (standard deviation) was 207.5 (145.6) mg/day at the baseline. When examining the association with the four physical fitness parameters, higher taurine intake positively increased the change in knee extension muscle strength (T1; 0.1, T2; 0.8, T3; 1.1 (kgf) GLM, p < 0.05; p for trend <0.05) and reduced the decline in knee extension muscle strength in the subgroup analysis of participants aged ≥65 years (T1: -1.9, T2: -1.7, T3: -0.4 kgf; GLM p < 0.05, p for trend <0.05). No relationship was found between taurine intake and the remaining three fitness factors. Conclusion: Estimation of taurine intake showed that dietary taurine intake potentially contributes to the maintenance of knee extension muscle strength over 8 years among Japanese community-dwelling middle-aged and older individuals. This is the first study to investigate the association of dietary taurine intake with muscle strength.

Identification of Potential Blood-Based Biomarkers for Frailty by Using an Integrative Approach.

INTRODUCTION: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive, and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty. METHODS: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA-sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65-90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study. RESULTS: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79-0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch's t test p < 0.001). CONCLUSION: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use.

Associations of dietary patterns and longitudinal brain-volume change in Japanese community-dwelling adults: results from the national institute for longevity sciences-longitudinal study of aging.

BACKGROUND: The association of dietary patterns and longitudinal changes in brain volume has rarely been investigated in Japanese individuals. We prospectively investigated this association in middle-aged and older Japanese community-dwelling adults. METHODS: Data with a 2-year follow-up from the sixth wave (July 2008 to July 2010; baseline) to the seventh (July 2010 to July 2012; follow-up) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project were analyzed. Dietary intake was assessed using a 3-day dietary record, and longitudinal volume changes (%) in the total gray matter (TGM), total white matter, and frontal, parietal, occipital, temporal, and insular lobes were assessed using 3-dimensional T1 magnetic resonance imaging scans. Multiple factor analysis and hierarchical clustering revealed sex-specific dietary patterns. Associations between dietary patterns and annual brain-volume changes (%) were evaluated using general linear models adjusted for age, apoprotein E genotype, body mass index, medical history, lifestyle behaviors, socioeconomic factors, and energy intake. RESULTS: Among the 1636 participants (age: 40.3-89.2 years), three dietary patterns were determined for men (n = 815; Western; Vegetable-Fruit-Dairy; and Traditional Japanese diets) and women (n = 821; Western; Grain-Vegetable-Fruit; and Traditional Japanese diets). Compared to women following the Western diet, those on the Traditional Japanese diet had less TGM atrophy. Multivariable-adjusted ß (95% confidence interval) of the annual change (%) of TGM was - 0.145 (-0.287 to -0.002; P = 0.047), which correlated with reduced parietal lobe atrophy. No association between dietary pattern and brain atrophy was observed in men. CONCLUSIONS: Adherence to healthy dietary patterns, with higher consumption of whole grains, seafood, vegetables, fruits, mushrooms, soybean products, and green tea, potentially confers a protective effect against brain atrophy in middle-aged and older Japanese women but not in men. Further research to confirm these results and ascertain the underlying mechanisms is required. This study highlights the importance of sex-specific effects on the relationship between dietary patterns and brain health in diverse populations.

Higher-level competence: Results from the Integrated Longitudinal Studies on Aging in Japan (ILSA-J) on the shape of associations with impaired physical and cognitive functions.

AIM: This study aimed to examine the relationships between levels of competence and impaired physical and cognitive functions in older adults. METHODS: We used a data set of the Integrated Longitudinal Studies on Aging in Japan for 2017 including 5475 community-dwelling older adults. Levels of competence were assessed using the Japan Science and Technology Agency Index of Competence (JST-IC). Grip strength (low grip strength: <28 kg for men and <18 kg for women) and gait speed (slow gait speed: <1.0 m/s for both sexes) were evaluated as physical function measurements, and the Mini-Mental State Examination (cognitive decline: <24 on the Mini-Mental State Examination) was used to assess cognitive function. RESULTS: The JST-IC had areas under the curve estimated from receiver operating characteristic analysis ranging from 0.65 to 0.73 for detecting low function as assessed by these tests. Restricted cubic spline curves showed that the shape of the association between the JST-IC and impaired function depended on sex and the test used. The comparison between perfect and imperfect JST-IC scores showed significant differences in the prevalence of low grip strength in both sexes, slow gait speed in women, and cognitive decline in men. CONCLUSIONS: It may be insufficient to identify those with impaired physical or cognitive function using the JST-IC. The shape of the association with the JST-IC varies across their measurements. Our findings can help interpret JST-IC scores in the context of low physical and cognitive functions. Geriatr Gerontol Int 2024; 24: 352-358.

Association between abdominal adiposity and cognitive decline in older adults: a 10-year community-based study.

OBJECTIVES: This study aimed to investigate the association between abdominal adiposity and change in cognitive function in community-dwelling older adults. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging. MEASUREMENTS: Cognitive function was evaluated biennially using the Mini-Mental State Examination (MMSE) over 10 years. Waist circumference (WC) was measured at the naval level, and subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed using baseline computed tomography scans. WC, SFA, and VFA areas were stratified into sex-adjusted tertiles. A linear mixed model was applied separately for men and women. RESULTS: This study included 873 older adults. In men, the groups with the highest levels of WC, SFA, and VFA exhibited a greater decline in MMSE score than the groups with the lowest levels (ß [95% confidence interval]: WC, -0.12 [-0.23 to -0.01]; SFA, -0.13 [-0.24 to -0.02]; VFA, -0.11 [-0.22 to -0.01]). In women, the group with the highest level of WC and SFA showed a greater decline in MMSE score than the group with the lowest level (WC, -0.12 [-0.25 to -0.01]; SFA, -0.18 [-0.30 to -0.06]), but VFA was not associated with cognitive decline. CONCLUSION: Higher WC, SFA, and VFA in men and higher WC and SFA in women were identified as risk factors for cognitive decline in later life, suggesting that abdominal adiposity involved in cognitive decline may differ according to sex.

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.

Differential Longitudinal Associations Between Domains of Cognitive Function and Physical Function: A 20-Year Follow-Up Study.

OBJECTIVES: Cognitive and physical functions are both associated with disability and death. Recent studies have addressed the relationship between cognitive declines and physical declines; however, whether various facets of cognition are diversely associated with specific physical functions is yet to be ascertained. The present work examines the longitudinal associations between fluid and crystallized cognitive functions (Gf and Gc) and physical functions. METHODS: The sample consisted of 863 community-dwelling older adults (baseline age 60-79 years) from the National Institute for Longevity Sciences-Longitudinal Study of Aging. The participants were tested on a set of Gf and Gc tests and physical tests (grip strength and gait speed). We ran a series of Multivariate Latent Growth Curve models. Specifically, we tested the relationship between cognitive and physical functions in terms of baseline performance (intercept) and rate of change (slope). RESULTS: The slope-slope correlations between Gf and physical function were large (grip strength r = 0.64 and gait speed r = 0.68, ps < .001). By contrast, the slope correlations between Gc and physical functions were weak (rs ≤ 0.31) and barely or marginally significant (ps ≤ .06). DISCUSSION: The results show that distinct domains of cognitive functions have different associations with physical functions. Namely, the aging-associated declines in the tested physical functions are robustly correlated with the declines in Gf, but are only weakly correlated with the declines in Gc. Therefore, Gc measures may be poor proxies for the patient's frailty and should be considered with caution in clinical assessment.

Effects of cigarette smoking and secondhand smoke exposure on physical frailty development among community-dwelling older adults in Japan: Evidence from a 10-year population-based cohort study.

AIM: This study explored longitudinally the relationship between smoking and secondhand smoke and the incidence of physical frailty in community-dwelling Japanese older people. METHODS: Data collected from the National Institute for Longevity Sciences-Longitudinal Study of Aging database from 2002 to 2012 (third to seventh wave) among older adults aged ≥65 years were analyzed. Participants with physical frailty at baseline, as determined by the Cardiovascular Health Study criteria, missing data or who failed to attend follow ups were excluded. Data on current cigarette smoking and secondhand smoke exposure were collected from the third wave results. The generalized estimating equation model was used to examine the longitudinal relationships between smoking, secondhand smoke and subsequent frailty. RESULTS: The final analysis included 540 participants with a mean age of 71.4 years (standard deviation 4.6). The generalized estimating equation analysis showed that, compared with non-smokers, smokers were at significant risk of physical frailty (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.21-4.74) after adjustment for multiple covariates; especially men (OR 3.75, 95% CI 1.76-8.00) and older adults aged ≥75 years (OR 4.12, 95% CI 1.43-11.87). Participants exposed to both smoking and secondhand smoke had a higher risk of physical frailty (OR 3.47, 95% CI 1.56-7.73) than non-smokers without secondhand smoke exposure. Smokers exposed to secondhand smoke were associated with more risk of physical frailty (OR 9.03, 95% CI 2.42-33.77) compared with smokers without secondhand smoke exposure. CONCLUSIONS: Smoking, especially when combined with secondhand smoke exposure, is associated with future physical frailty among older adults. Geriatr Gerontol Int 2024; 24: 142-149.

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.

Relationship between quadriceps muscle computed tomography measurement and motor function, muscle mass, and sarcopenia diagnosis.

Background: The quadriceps muscle is one of the human body's largest and most clinically important muscles and is evaluated using mid-thigh computed tomography (CT); however, its relationship with motor function and sarcopenia remains unclear. Herein, we investigated the relationship between the cross-sectional area (CSA) of the quadriceps muscle, CT attenuation value (CTV), dual-energy X-ray absorptiometry muscle mass measurements, and muscle strength and motor function to evaluate the relationship between muscle mass loss and motor function decline, determine the diagnostic ability for sarcopenia, and confirm the usefulness of quadriceps muscle CT evaluation. Methods: A total of 472 middle-aged and older community dwellers (254 men and 218 women) aged ≥40 years (mean age: 62.3 years) were included in this study. The quantity and quality of the quadriceps muscle were assessed using CSA and CTV (CSA×CTV) as a composite index multiplied by quality and quantity. Age-adjusted partial correlations by sex with eight motor functions (knee extension muscle strength, power, normal walking speed, fast walking speed, grip strength, sit-up ability, balance ability, and reaction time) were evaluated, including correction methods for height, weight, and body mass index (BMI). Further, the accuracy of sarcopenia diagnosis was evaluated using appendicular muscle mass with dual-energy X-ray absorptiometry measurements, grip strength, and walking speed as the gold standard, and receiver operating characteristic curves were plotted to evaluate diagnostic performance. Results: In men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p<0.05), excluding only balance ability. BMI-corrected CSA was significantly correlated with all eight motor functions in men and women (p<0.05). In the diagnosis of sarcopenia based on skeletal muscle index, CSA (area under the curve (AUC) 0.935) and CSA×CTV (AUC 0.936) and their correction by height (CSA/height (AUC 0.917) and CSA×CTV/height (AUC 0.920)) were highly accurate and useful for diagnosis in men but moderately accurate in women (CSA (AUC 0.809), CSA×CTV (AUC 0.824), CSA/height (AUC 0.799), CSA×CTV/height (AUC 0.814)). Conclusion: The present results showed that a single CT image of the quadriceps muscle at the mid-thigh is useful for diagnosing sarcopenic changes, such as loss of muscle mass, muscle weakness, and muscle function.