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Background: Several circulating microRNAs (miRNAs) in the blood are indicators of chronic diseases, but their association with multimorbidity burden is unknown. The aim of this study was to assess the association of plasma levels of circulating miR-323–3p and miR-135–3p with age, cognitive performance, and number of comorbidities in middle-aged and older individuals. Methods: Data from 295 community dwellers (≥40 years) who participated in the second wave (2000‒2002) of the National Institute for Longevity Sciences-Longitudinal Study of Aging in Japan were analyzed. miRNAs were isolated from the plasma, and miR-323–3p and miR-135–3p levels were measured using quantitative reverse-transcription polymerase chain reaction and normalized, with miR-16 as an endogenous reference gene. Cognitive performance was assessed using the Information and Similarities subtests and the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale-Revised Short Form (WAIS-R-SF). Correlation tests and multivariate general linear regression analyses were performed to examine the relationship among circulating miRNA levels, burden of multimorbidity, and cognitive performance. Results: The mean age of the participants was 59.15 ± 10.26 years. Pearson's correlation analysis revealed that the miR-323–3p level positively correlated with age and number of comorbidities but negatively correlated with WAIS-R-SF subtest performance. In men, miR-323–3p level negatively correlated with the performance of all three WAIS-R-SF subtests. The general linear regression analysis showed that the miR-323–3p level increased in participants with four comorbidities compared with those with one comorbidity. Conclusion: Circulating miR-323–3p level is associated with the burden of multimorbidity and decreased cognitive performance in middle-aged and older adults.

Abstract 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 0.05). 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

Objectives: Variability in intrinsic capacity (IC) changes among community-dwelling older adults and their effect on health outcomes remain understudied. We examined the variability in IC trajectories and their impact on higher-level functional capacity (HLFC), life satisfaction, and self-esteem. Design: Longitudinal study. Setting: Data from the second to seventh waves (2000–2012) of the National Institute for Longevity Sciences–Longitudinal Study of Aging project. Participants: 934 community dwellers (aged ≥60). Measurements: We used group-based multi-trajectory modeling to obtain IC trajectories across six domains: cognition, locomotion, vitality, vision, hearing, and psychological well-being. We employed multivariable regression to investigate the associations between IC trajectories and a decline in HLFC (assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence [TMIG-IC]; baseline TMIG-IC - follow-up TMIG-IC ≥ 2; logistic regression model), life satisfaction (assessed using the Life Satisfaction Index-K [LSI-K]; linear mixed model), and self-esteem (assessed using the Rosenberg Self-Esteem Scale [RSES]; linear mixed model). Results: We identified four IC trajectories: the “healthy aging group” (63.7%), the “hearing decline group” (15.1%), the “vision and cognitive decline group” (12.7%), and the “comprehensive deterioration group” (8.5%). Compared to the healthy aging group, the vision and cognitive decline group and the comprehensive deterioration group displayed a significantly greater risk of a decline in the TMIG-IC score (multivariable-adjusted odds ratio [aOR], 95% confidence interval [CI] = 2.05 [1.11, 3.79], 2.74 [1.41, 5.30], respectively), the LSI-K score (multivariable-adjusted β [standard error] = −0.46 [0.08], −0.52 [0.10], respectively), and the RSES score (multivariable-adjusted β [standard error] = −0.85 [0.16], −0.66 [0.20], respectively). The “hearing decline group” did not show a significantly increased risk for these outcomes. Conclusion: Older adults with different IC trajectories may differ in HLFC, life satisfaction, and self-esteem. Public health officials should be aware of this and provide targeted interventions.

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

BackgroundNutritional 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.MethodsThe 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.ResultsThe 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.ConclusionThese 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.

Abstract 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 β (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.

Abstract 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,

Abstract Background Prior study reported that mushroom consumption was associated with a lower incidence of hyperuricemia, but there is limited evidence on this association. We conducted a collaborative study to investigate the association between mushroom intake and hyperuricemia in middle-aged and older populations. Methods We used data from the National Health and Nutrition Examination Survey (NHANES) in the U.S. (2007–2018) and the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan (1997–2012). Consumption of mushroom (g/day) were measured by one- or two-day dietary recall in NHANES and by 3-day dietary records in the NILS-LSA. Hyperuricemia was defined using uric acid levels as > 420 μmol/L and > 350 μmol/L in NHANES for men and women, respectively; in the NILS-LSA, serum uric acid was repeatedly measured at baseline and follow-up surveys. Hyperuricemia was defined as uric acid levels > 416.4 μmol/L for men and ≥ 356.9 μmol/L for women. Logistic regression models in NHANES (cross-sectionally) and Generalized Estimation Equations in NILS-LSA (longitudinally) were performed. Results A total of 5,778 NHANES participants (mean (SD) age: 53.2 (9.6) years) and 1,738 NILS-LSA (mean (SD) age: 53.5 (11.2) years) were included. Mushrooms were consumed by 5.7% of participants in NHANES and 81.2% in NILS-LSA. We did not observe a significant association between mushroom intakes and hyperuricemia in the NHANES men and women. However, in the NILS-LSA, compared to non-consumers, a higher mushroom intake was associated with a lower risk of incident hyperuricemia in men under 65 years old. The adjusted odds ratio (95% CI) for non-consumers, participants with middle, and the highest consumption of mushrooms were 1.00 (Ref.), 0.77 (0.44, 1.36), and 0.55 (0.31, 0.99), respectively (P-trend = 0.036). No association was found in women in NILS-LSA. Conclusions Mushroom consumption was associated with a lower risk of incident hyperuricemia in Japanese men.

Abstract Background Sleep duration and amino acid intake are independently associated with cognitive decline. This study aimed to determine the longitudinal association between sleep duration and cognitive impairment incidence and to examine the involvement of diet, particularly amino acid intake, in these associations in community dwellers. Methods In this longitudinal study in a community-based setting, we analyzed data from 623 adults aged 60–83 years without cognitive impairment at baseline. Sleep duration was assessed using a self-report questionnaire. Amino acid intake was assessed using 3-day dietary records. Cognitive impairment was defined as a Mini-Mental State Examination score ≤ 27. Participants were classified into short-, moderate-, and long-sleep groups according to baseline sleep duration (≤ 6, 7–8, and > 8 h, respectively). Using moderate sleep as a reference, odds ratios (ORs) and 95% confidence intervals (CIs) of short- and long-sleep for cognitive-impairment incidence were estimated using the generalized estimating equation. Participants were classified according to sex-stratified quartiles (Q) of 19 amino acid intake: Q1 and Q2–Q4 were low- and middle to high-intake groups, respectively. Using middle- to high-intake as a reference, ORs and 95% CIs of low intake for cognitive impairment incidence were estimated using the generalized estimating equation in each sleep-duration group. Follow-up period, sex, age, body mass index, depressive symptoms, education, smoking status, employment status, sleep aids use, physical activity, medical history, and Mini-Mental State Examination score at baseline were covariates. Results Mean follow-up period was 6.9 ± 2.1 years. Adjusted ORs (95% CIs) for cognitive impairment in short- and long-sleep groups were 0.81 (0.49–1.35, P = 0.423) and 1.41 (1.05–1.87, P = 0.020), respectively. Particularly in long sleepers (i.e., > 8 h), cognitive impairment was significantly associated with low cystine, proline, and serine intake [adjusted ORs (95% CIs) for cognitive impairment were 2.17 (1.15–4.11, P = 0.017), 1.86 (1.07–3.23, P = 0.027), and 2.21 (1.14–4.29, P = 0.019), respectively]. Conclusions Community-dwelling adults aged ≥ 60 years who sleep longer are more likely to have cognitive decline, and attention should be paid to the low cystine, proline, and serine intake.

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 (β [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.

IntroductionTaurine 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.MethodsParticipants 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.ResultsThe 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

BackgroundThe 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.MethodsA 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.ResultsIn men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p

Background This study evaluated the chronological changes in physical and cognitive functions in middle-aged and older adults with and without rheumatoid arthritis (RA). Methods This population-based case-control longitudinal study included individuals aged 40–79 years at baseline who agreed to participate. We identified 42 participants with RA and randomly selected 84 age- and sex-matched controls. Physical function was assessed according to gait speed, grip strength, and skeletal muscle mass. Cognitive function was assessed based on the information, similarities, picture completion, and digit symbol substitution test scores of the Wechsler Adult Intelligence Scale-Revised Short Form. The general linear mixed models comprised the fixed effects of the intercept, case, age, time in years since baseline, and case×time interaction, which were used to examine longitudinal changes in physical and cognitive functions. Results Regardless of RA status, grip strength decreased and the picture completion score increased in the group aged

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

Abstract Background Vitamin D is an essential nutrient in musculoskeletal function; however, its relationship to sarcopenia remains ambiguous, and the mechanisms and targets of vitamin D activity have not been elucidated. This study aimed to clarify the role of vitamin D in mature skeletal muscle and its relationship with sarcopenia. Methods This epidemiological study included 1653 community residents who participated in both the fifth and seventh waves of the National Institute for Longevity Sciences, Longitudinal Study of Aging and had complete background data. Participants were classified into two groups: vitamin D‐deficient (serum 25‐hydroxyvitamin D

Background We conducted a study to investigate the relationship between optic nerve vertical cup-to-disc ratio (VCDR), body and ocular parameters, and brain lesions in middle-aged and above Japanese subjects, because although various risk factors for glaucoma have been previously characterised, it is theorised that there are unidentified neurological components.Methods In this population-based, age/gender-stratified, cross-sectional study that involved 2239 Japanese subjects (1127 men and 1112 women) aged 40 years and older (mean age: 59.3±11.7 years) living in the central geographical region of Japan who participated in the National Institute of Longevity Sciences–Longitudinal Study of Aging between 2002 and 2004, 4327 eyes and 2239 obtained MRIs of the head were evaluated. Multivariate mixed model and trend analyses were also performed.Results No significant relationship between VCDR and brain lesions, other than basal ganglia lesions, was found. VCDR significantly increased with the high grade of basal ganglia infarct lesions (p=0.0193) and high intraocular pressure (p

Background: Short-chain fatty acids (SCFAs) have been suggested to be associated with skeletal muscle mass maintenance. However, the role of dietary SCFAs in preserving muscle strength in the older population remains unclear. Objectives: To clarify the longitudinal association between the dietary intake of SCFAs and the development of low muscle strength in older community dwellers. Methods: Data were obtained from the National Institute for Longevity Sciences-Longitudinal Study of Aging cohort. The participants included 441 men and 382 women who participated in the baseline survey (the fifth wave, between 2006 and 2008) and at least one follow-up examination (sixth to ninth waves, between 2008 and 2022) and were ≥60 years old and did not have low muscle strength (defined as a grip strength of

Background and aims: Carriers of the apolipoprotein E ε4 allele (APOEɛ4) have an increased risk of developing dementia (e.g., Alzheimer's disease). However, it is less clear whether the APOEɛ4 might also be involved in cognitive aging among the non-clinical population of older adults. While some studies have suggested that the APOEɛ4 is related to accelerated cognitive decline in the normal aging process, others have failed to provide compelling evidence of such an impact. Notably, these discrepancies may depend on methodological shortcomings, including short time spans, few assessments, and small sample sizes. The present study overcomes the above limitations and aims to clarify the impact of the APOEɛ4 genotype on long-term longitudinal changes in cognitive functions in middle-aged and older adults in Japan. Methods and results: The data were retrieved from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) survey (N = 1832; 40 to 79 years of age at baseline). The participants were tested over nine waves covering a period of approximately 20 years. Latent Growth Curve (LGC) modeling was employed to test the impact of the interaction between APOEɛ4 status and age on several cognitive functions. Four tests of the WAIS-R were administered: Information, Similarities, Picture completion, and Digit Symbol Substitution Test (DSST). The results showed that the APOEɛ4 carriers experienced a more pronounced decline in the DSST (p = 0.001) and Similarities (p = 0.022) tests. A similar tendency was found in the Information test (p = 0.034). By contrast, no effect was found in the Picture completion test (p = 0.563). Conclusions: APOEɛ4 carriers seem to exhibit a steeper cognitive decline, which becomes apparent in old age. This effect is more robust in fluid cognitive skills (DSST) than crystallized cognitive skills (Information and Similarities). Overall, the APOEɛ4 genotype may be a significant risk factor in normal (i.e., non-clinical) cognitive aging.

Abstract Background Although muscle quality evaluations are currently considered important for diagnosing sarcopenia, data from the general population are lacking. This study used mid‐thigh computed tomography measurements to evaluate age‐related and sex‐related differences in quadriceps femoris muscle quality and mass and their relationships with knee extension strength (KES). Methods Cross‐sectional data from 520 Japanese individuals (273 men and 247 women, mean age: 63.1 ± 10.6 years) were analysed. Mass and quality were assessed using quadriceps cross‐sectional areas (CSAs) and computed tomography values (CTVs), respectively. The four constituent muscles, intermuscular adipose tissue, and entire quadriceps area (total quadriceps muscles + intermuscular adipose tissue) were assessed, and the data were stratified by five age groups and sex. To evaluate age‐related decline, linear and quadratic equations were tested for fit according to the constituent muscles and sex. KES could be measured in 472 of the 520 participants (254 men and 218 women, mean age: 62.3 ± 10.3). Multiple linear regression analyses with age‐adjusted models were then used for evaluating the relationships between KES and quadriceps measurements. Results All muscle CSAs and CTVs showed downward trends with age (men: P

Abstract Background There is a growing interest in the significance of adopting a variety of lifestyle habits for maintaining cognitive function among older adults. A lifestyle that is easy to modify, simple, and less burdensome for older people is ideal. We investigated the longitudinal association between global cognitive decline and cognitive leisure activities (CLAs) combined with long-chain polyunsaturated fatty acids (LCPUFAs) intake. Methods The National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) enrolled community-dwelling middle-aged and older men and women who were randomly selected from Obu-City and Higashiura Town, Aichi, Japan. Baseline data (2006–2008), including CLAs and dietary intake, were obtained from 517 participants (aged 60–84 years) with normal cognition. Global cognitive decline, defined as the Mini-Mental State Examination (MMSE) score ≤ 27, was assessed at baseline and four years later. Interaction between CLAs and LCPUFAs on cognitive decline was investigated using a multiple logistic analysis with adjustment for confounders. CLA engagement and LCPUFA intake were divided into high and low groups according to the frequency at which each participant engaged in the activity and the median intake level according to sex, respectively. Results A significant interaction was detected for the combination of CLA engagement and LCPUFA intake. Logistic regression coefficients revealed significant interactions when participants engaged in more than five CLA varieties. One of the CLAs, art appreciation, produced a significant main effect against cognitive decline and a significant interaction in combination with LCPUFA intake. The major LCPUFAs—docosahexaenoic acid and arachidonic acid—also exhibited a significant interaction. The combination of high LCPUFA intake and high art appreciation frequency yielded a lower adjusted odds ratio for cognitive decline than the combination of low LCPUFA and low art appreciation [0.25 (95 % confidence intervals, 0.11–0.56)]. Conclusions Preserving cognitive function might be associated with a combination of varied and high-frequency engagement in CLAs combined with high LCPUFA intake.

This study aimed to investigate the effect of cognitive reserve (CR) on the rate of cognitive decline and cerebral glucose metabolism in amnestic mild cognitive impairment (MCI) using the Study on Diagnosis of Early Alzheimer’s Disease-Japan (SEAD-J) dataset. The patients in SEAD-J underwent cognitive tests and fluorodeoxyglucose-positron emission tomography (FDG-PET). MCI to be studied was classified as amnestic MCI due to Alzheimer’s disease (AD) with neurodegeneration. A total of 57 patients were visually interpreted as having an AD pattern (P1 pattern, Silverman’s classification). The 57 individuals showing the P1 pattern were divided into a high-education group (years of school education ≥13, N = 18) and a low-education group (years of school education ≤12, N = 39). Voxel-based statistical parametric mapping revealed more severe hypometabolism in the high-education group than in the low-education group. Glucose metabolism in the hippocampus and temporoparietal area was inversely associated with the years of school education in the high- and low-education groups (N = 57). General linear mixed model analyses demonstrated that cognitive decline was more rapid in the high-education group during 3-year follow-up. These results suggest that the cerebral glucose metabolism is lower and cognitive function declines faster in patients with high CR of amnestic MCI due to AD defined by FDG-PET.

Abstract Background Components of physical frailty cluster into subtypes, but it remains unknown how these might be associated with age‐related functional declines and multimorbidities. This study aims to investigated associations of physical frailty subtypes with functional declines and multimorbidity in a 10 year longitudinal cohort survey. Methods Complementary longitudinal cohort study used group‐based multitrajectory modelling to verify whether frailty subtypes discovered in Taiwan are presented in another aging cohort, then investigated associations of these subtypes with cognitive decline and multimorbidity. Participants aged ≥50 years were recruited from the third to sixth waves (May 2002 to July 2010) of the National Institute for Longevity Sciences‐Longitudinal Study of Aging, in Japan. People with incomplete data, pre‐frail/frail status before their index wave, and those with incomplete data or who died during follow‐up, were excluded. Group‐based trajectory analysis denoted five established physical frailty criteria as time‐varying binary variables in each wave during follow‐up. Incident frailty was classified as mobility subtype (weakness/slowness), non‐mobility subtype (weight loss/exhaustion), or low physical activity subtype. General linear modelling investigated associations of these frailty subtypes with activities of daily living, digit symbol substitution test (DSST) and Charlson Comorbidity Index (CCI) at 2 year follow‐up. Results We identified four longitudinal trajectories of physical frailty, which corroborated the distinct subtypes we discovered previously. Among 940 eligible participants, 38.0% were robust, 18.4% had mobility subtype frailty, 20.7% non‐mobility subtype, and 20.1% low physical activity subtype. People with mobility subtype frailty were older than those with other frailty subtypes or robust status and had higher prevalence of hypertension, diabetes, and heart failure. In the multivariable‐adjusted general linear models, mobility‐subtype frailty was associated with a significantly lower DSST score (point estimate −2.28, P = 0.03) and higher CCI (point estimate 0.82, P

This study explores the clusters of work–family balance (WFB) among Japanese middle-aged and older adults and clarifies the characteristics of the derived clusters. Data on working adults (N = 1,351; age range = 40–85 years) were drawn from a pool of participants in the National Institute for Longevity Sciences—Longitudinal Study of Aging. The WFB scale consists of subscales assessing work–family conflict (WFC) and work–family facilitation (WFF). First, a cluster analysis was performed using the WFB scale, and four clusters were extracted. Second, we examined associations between the four clusters and related variables such as demographic characteristics, work, family, and lifestyle factors, social support, and mental health. Our findings showed that the clusters included high-WFC/high-WFF, high-WFC/low-WFF, low-WFC/high-WFF, and low-WFC/low-WFF. Differences were found in related variables among the clusters. Specifically, those in the Low-WFC/High-WFF cluster had a good lifestyle, received the highest levels of social support, and had the fewest mental health issues. Our findings have implications for maintaining sufficient WFB and promoting positive mental health among workers.

Brain reserve is a topic of great interest to researchers in aging medicine field. Some individuals retain well-preserved cognitive function until they fulfill their lives despite significant brain pathology. One concept that explains this paradox is the reserve hypothesis, including brain reserve that assumes a virtual ability to mitigate the effects of neuropathological changes and reduce the effects on clinical symptoms flexibly and efficiently by making complete use of the cognitive and compensatory processes. One of the surrogate measures of reserve capacity is brain volume. Evidence that dementia and hearing loss are interrelated has been steadily accumulating, and age-related hearing loss is one of the most promising modifiable risk factors of dementia. Research focused on the imaging analysis of the aged brain relative to auditory function has been gradually increasing. Several morphological studies have been conducted to understand the relationship between hearing loss and brain volume. In this mini review, we provide a brief overview of the concept of brain reserve, followed by a small review of studies addressing brain morphology and hearing loss/hearing compensation, including the findings obtained from our previous study that hearing loss after middle age could affect hippocampal and primary auditory cortex atrophy.

Abstract Background Although our previous study using a food frequency questionnaire simulated nutritional characteristics of the traditional Japanese diet, this issue has not been sufficiently evaluated. This study was conducted to examine the relationship between the traditional Japanese diet and nutrient density (ND). Methods A cross-sectional study employing the dietary record method was conducted among 2221 community-dwelling Japanese adults (40–88 years) living in Aichi Prefecture, Japan, in 2006–2008. Based on previous studies, a 9-component Japanese Diet Index (JDI) and a 12-component modified JDI (mJDI12) were defined. To develop a new weighted index, a multiple linear regression model was used to select food components which were significantly associated with an ND score (integrated by 11 nutrient components) from the mJDI12 and weight them. Correlation analyses were performed between JDI, mJDI12, the new weighted JDI score and the ND score and its 11 nutrient components. The findings were validated with data from 2008 to 2010 by assessing the associations between the JDIs scores and the ND score. Results Scores of the JDI and mJDI12 were positively correlated with the ND score (corresponding Spearman’s ρ [95% confidence interval; CI], 0.34 [0.31, 0.38] and 0.44 [0.41, 0.48], respectively; P

Abstract Background The gait speed and handgrip strength represented the core determinants of physical frailty and sarcopenia, which were reported to be associated with cognitive impairment and decline. Different physical measures might differentially affect cognitive changes, such as higher-level cognitive change and global cognitive decline. This study examined the differential associations of gait speed and handgrip strength with 10-year cognitive changes among community-dwelling older people. Methods Participants aged 60 years and over living in the community were invited for study. Gait speed and handgrip strength were classified into 5 groups based on quintiles at baseline. Cognitive functions were assessed using the Mini-Mental State Examination (MMSE) and Digit Symbol Substitution Test (DSST) every 2 years from baseline for a period of 10 years. Linear mixed effects models were used to determine the role of gait speed and handgrip strength in the prediction of 10-year cognitive changes by adjusting covariates, including age, gender, education, depressive symptoms, marital status, smoking status, instrumental activities of daily life (IADL), Charlson Comorbidity Index (CCI), and body mass index (BMI) at baseline. Results A total of 1096 participants were enrolled in the study. The mean age was 69.4 ± 5.8 years and 50.9% were male. The slowest gait speed group showed a significantly greater decline in the DSST scores over 10 years than the highest group (estimate = 0.28 and P = 0.003), but not in the MMSE scores (estimate = 0.05 and P = 0.078). The lowest handgrip strength group showed a significantly greater decline in the MMSE scores than the highest group (estimate = 0.06 and P = 0.039) and in the DSST scores than the highest two quintiles (estimate = 0.20 and P = 0.033 for the fourth quintile; estimate = 0.20 and P = 0.040 for the highest quintile) over 10-year follow-up. Conclusions A slow gait speed could predict 10-year cognitive decline using DSST, and a low handgrip strength could predict 10-year cognitive decline using MMSE in addition to DSST. Thus both physical measures are lined to cognitive decline but there may be different mechanisms between brain and physical functions.

Abstract Background Hyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear. The present study aimed to clarify the association between blood glucose levels and information processing ability in middle-aged and older adults. Methods The subjects were 866 men and 815 women aged 40–79 years not taking medication for diabetes who participated in the first study wave (1997–2000) and then participated at least once in the subsequent six study waves (2000–2012) of the National Institute for Longevity Sciences—Longitudinal Study of Aging, Japan. Hemoglobin A1c (HbA1c) levels were categorized into four groups (

We investigated the associations between hearing aids (HA) and the maintenance of cognitive function among community-dwelling older adults with moderate hearing loss. A total of 407 participants aged 60 years or older with moderate hearing loss were recruited from the National Institute for Longevity Sciences, Longitudinal Study for Aging (NILS-LSA). Moderate hearing loss was defined as a pure-tone average of 40-69 dB at 500, 1000, 2000, and 4000 Hz of the better ear, according to the definition proposed by the Japan Audiological Society. Cognitive function was evaluated using the four subtests of the Japanese version of the Wechsler Adult Intelligence Scale-Revised Short Forms (WAIS-R-SF): Information, Similarities, Picture completion, and Digit Symbol Substitution (DSST). A longitudinal analysis of 1192 observations with a mean follow-up period of 4.5 ± 3.9 years was performed. The HA use rate at any time during the follow-up period was 31.4%, and HA users were significantly younger (t-test, p = 0.001), had worse hearing (p < .0001) and higher education (p = 0.001), participated more frequently in the survey (p < .0001), and were less depressed (χ2 test, p = 0.003) than the older adults not using HA. General linear mixed models consisted of the fixed effects of HA use, follow-up time, and an HA use × time interaction term adjusted for age and pure-tone average thresholds at baseline, sex, education, and other possible confounders. HA use showed significant main effects on the scores for Picture completion and DSST after adjustment; scores were better in the HA use group than in the no HA use group. The HA use × time interaction was significant for the Information score (p = 0.040). The model-predicted 12-year slope with centralizing age indicated that the no HA use group showed greater decline over time on Information scores than did HA use group. The slopes did not differ between HA users and non-users for the Similarities, Picture completion and DSST. In conclusion, HA use may have a protective effect on the decline in general knowledge in older adults with moderate hearing loss.

Abstract Background Age-related declines in skeletal muscle mass and strength, representing “sarcopenia,” are a growing concern in aging societies. However, the prevalence of low muscle mass based on the height2-adjustment has been shown to be extremely low, and a more appropriate definition of low muscle mass is needed, particularly for Asian women. The aim of this study was to explore the most appropriate adjustment of appendicular lean mass (ALM) for predicting mortality or disability risk using ALM or any of 5 adjustments of ALM among community-dwelling Japanese. Methods Subjects comprised 1026 men and 952 women between 40 and 79 years old at baseline (1997–2000) who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging, Japan. ALM (kg) and 5 adjusted indices of ALM (ALM/leg length, ALM/height, ALM/height2, ALM/weight, and ALM/body mass index [BMI]) were assessed at baseline. Disability was defined by long-term care insurance certification based on responses to a survey mailed in 2013, and death records were obtained as vital statistics until December 2014. Crude and adjusted Cox proportional hazard models were used to estimate hazard ratios for mortality or disability by sex-stratified quintiles of each ALM index (ALM and adjusted ALM) or sarcopenia-related indices. The area under the curve (AUC) was calculated with the multivariate-adjusted logistic regression model. Additionally, mixed-effects analyses were used to clarify the age-related ALM indices decline over 12 years (n = 1838). Results Crude Cox proportional hazard models and multivariate-adjusted logistic model (AUC) indicated that higher ALM and ALM/BMI in women, and higher ALM, ALM/leg length, ALM/height, and ALM/BMI in men were associated with lower risks for mortality or disability than ALM/height2. The mixed effect model indicated all ALM indices in men, and ALM, ALM/leg length, and ALM/height in women could better predict age-related lean muscle mass decline. Conclusions Unadjusted ALM in women, and ALM/leg length, ALM/height, ALM/BMI, and ALM in men may be more appropriate for predicting future mortality or disability than ALM/height2. Considering the age-related muscle mass decline, unadjusted ALM would be the first variable to assess, regardless of sex, in this Japanese cohort study.

This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living), and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997–2000) who participated in a follow-up postal survey (2013). Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role). The odds ratio (OR) and 95% confidence interval (CI) for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs) for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0–4, 5–6, 7–8 groups) were 1.00 (reference), 0.63 (0.44–0.92), and 0.54 (0.31–0.94). For the score of social role decline, multivariate adjusted ORs (95% CIs) were 1.00 (reference), 0.62 (0.40–0.97), and 0.46 (0.23–0.90), respectively (P for trend = 0.04). Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan.

A healthy elderly person may require nursing care after becoming frail, a condition characterized by slowness, weakness, exhaustion, low activity, and shrinking. Because few cohort studies have examined frailty in detail, the prevalence of frailty among the elderly in Japan is unclear. We examined the prevalence of frailty based on the frailty phenotype established by Fried using a large-scale cohort of randomly selected community-dwelling elderly in Japan. Participants included 871 elderly (446 men and 425 women) aged 65-91 years who participated in the sixth wave examination (July 2008 to July 2010) and seventh wave examination (July 2010 to July 2012) of the National Institute for Longevity Sciences - Longitudinal Study of Aging. The prevalence of shrinking, exhaustion, low activity, slowness, and weakness among the elderly participants was 10.2%, 38.6%, 21.1%, 11.4%, and 15.5%, respectively. The prevalence of frailty characterized by the limitations in 3 or more of these 5 domains was 8.5%. The prevalence of pre-frailty, characterized by limitations in 1 or 2 of 5 domains was 52.2%. Elderly who were diagnosed with frailty and pre-frailty included 3,086,000 people and 17,950,000 people, respectively. These data could contribute to the promotion of prevention and treatment strategies for frailty in Japan.

A growing body of literature has demonstrated that dementia and hearing loss are interrelated. Recent interest in dementia research has expanded to brain imaging analyses with auditory function. The aim of this study was to investigate the link between hearing ability, which was assessed using pure-tone audiometry, and the volume of brain regions, specifically the hippocampus, entorhinal cortex, Heschl’s gyrus, and total gray matter, using Freesurfer software and T1-weighted brain magnetic resonance imaging. The data for 2082 samples (age range = 40–89 years) were extracted from a population-based cohort of community dwellers. Hearing-impaired individuals showed significantly smaller hippocampal volumes compared with their non-hearing-impaired counterparts for all auditory frequency ranges. In addition, a correlational analysis showed a significant dose-response relationship for hearing ability and hippocampal volume after adjusting for potential confounding factors so that the more degraded the peripheral hearing was, the smaller the hippocampal volume was. This association was consistent through the auditory frequency range. The volume of the entorhinal cortex, right Heschl’s gyrus and total gray matter did not correlate with hearing level at any frequency. The volume of the left Heschl’s gyrus showed a significant relationship with the hearing levels for some auditory frequencies. The current results suggested that the presence of hearing loss after middle age could be a modifier of hippocampal atrophy.

Identification and modification of the risk factors for cognitive decline throughout the adult life span are priority subjects in a progressively aging society; however, much remains to be learned. The aim of this study was to understand whether changes in cognitive function can be affected by hearing impairment (HI) and whether the impact of HI differs depending on the cognitive domain. A total of 1,109 individuals aged 60 – 79 years at baseline who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences (NILS-LSA) was followed up for a maximum of 13.3 years. Cognitive function was evaluated using four subtests of the Japanese Wechsler Adult Intelligence Scale-Revised Short Forms: namely, Information, Similarities, Picture Completion, and the Digit Symbol Substitution subtests. The HI was defined as a pure-tone average of the better ear greater than 25 dB. A longitudinal analysis was performed of 4,437 observations obtained during a follow-up period of approximately 12 years. We estimated linear changes in subtest scores by HI status, using the time-varying mixed-effects regression model, which included fixed terms for the intercept, HI status at baseline, time (years elapsed since baseline), and an HI × time interaction term adjusted for age at baseline, sex, education, and other possible confounders. There were significant main effects of HI on the scores of the four subtests after adjustment. The HI × time interaction was significant for the scores of the Information (p = 0.001) and Digit Symbol Substitution subtests (p = 0.001). The scores of the HI group declined faster in the Information and Digit Symbol Substitution subtests compared to those of the no-HI group. The model-predicted 12-year slope using a mean baseline age (68.7 years) indicated no significant decline in the individuals without HI at baseline for the Information and Similarities subtests, however, this tolerance was lost in the individuals with HI. In conclusion, the present observation showed that the impact of HI on cognition was longitudinally significant and implied that the effect differs according to cognitive domain.

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. [ABSTRACT FROM AUTHOR]