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ABSTRACT: Objectives: To examine prevalence and risk factors for post-COVID-19 condition (PCC) in a paediatric population. Methods: The study included patients aged 5-17 years with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between 1 March 2021 and 30 April 2022 and matched non-infected controls from Yao City, Japan. We compared parent-reported symptoms persisting ≥2 months (present at 3 months post-infection for patients) between the groups. COVID-19 vaccination data was obtained from the Vaccination Registry. Results: Among 8167 invited individuals, 3141 (1800 cases, mean age: 10.4 years, 46.1% females; 1341 controls, mean age 10.5 years, 47.1% females) participated. Patients had elapsed average 273 (185-605) days from infection, and 1708 (94.9%) experienced mild acute symptoms. Patients had higher odds of having persistent symptoms than did controls (6.3% vs 2.2%, adjusted odds ratio [aOR]: 3.15, 95% confidence interval: 2.08-4.77), with 53.6% of them reporting current disruption due to the symptoms. Older age, low household income, pre-existing allergy, and autonomic nervous system disease were associated with increased risks of developing PCC; two prior vaccination doses reduced these risks (aOR: 0.52, 0.29-0.93). Conclusion: SARS-CoV-2 infection, including omicron infections heighten persistent symptom risk in the paediatric population, necessitating preventive strategies, notably vaccination.

Purpose: Although examining the dose-response curves of physical activity (PA) and sitting time with health-related outcomes is an important research agenda, the results for older Japanese adults are extremely limited. We examined the dose-response associations of PA and sitting time with all-cause mortality among older Japanese. Methods: Initially, 8,069 non-disabled residents (4,073 men; 3,996 women) aged 65–84 years of Ota City, Japan, were analyzed. Moderate-to-vigorous PA (MVPA) and sitting time were evaluated using the International Physical Activity Questionnaire-Short Form. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and sitting time for all-cause mortality were calculated, and the dose-response curves were examined using restricted cubic splines (RCS). Results: During 4.1 years of follow-up, 458 participants (5.7%; 331 men and 127 women) died. Compared with the low MVPA (3,000 METs·minutes/week) MVPA groups (moderate: HR 0.66; 95% CI, 0.54–0.82; high: HR 0.58; 95% CI, 0.45–0.75; P < 0.001 for trend). RCS showed that the HR for mortality reduced linearly up to approximately 2,000 METs·minutes/week of MVPA, and maximal risk reduction was seen at approximately 3,000–4,500 METs·minutes/week of MVPA. No significant dose-response association of sitting time with mortality was observed. Conclusion: Higher MVPA levels reduced all-cause mortality risk, in a significant inverse non-linear dose-response manner. Sitting time was not significantly associated with all-cause mortality. It is important to disseminate the significance of even a slight increase in the MVPA for reducing mortality risk.

Low back and knee pain, as major symptoms and early signs of osteoarthritis, have restricted healthy life expectancy, and numerous guidelines have recommended therapeutic exercise as the first-line treatment for chronic pain. Proportions of medical and exercise consultation use for those pain have been unclear, and these may change in the future. We performed a cross-sectional study of 2,954 persons aged over 30 years in 2017 as a part of the Circulatory Risk in Communities Study. A generalized linear model with logit link and 11-year age-group moving averages were used to estimate sex- and age-specific average proportions of lifetime pain, chronic pain, and dysfunctional chronic pain of the low back and knee, and history of medical and exercise consultation use. The medical consultation use increased in the order of lifetime pain, chronic pain, and dysfunctional chronic pain, reaching 69.1 % [65.2, 72.8] in women and 74.9 % [70.3, 79.0] in men for chronic low back pain, and 70.3 % [66.1, 74.2] in women and 55.6 % [49.3, 61.7] in men for chronic knee pain. On the other hand, the exercise consultation use accounted for 36.5 % [32.6, 40.6] in women and 28.8 % [24.4, 33.5] in men for chronic low back pain, and 40.8 % [36.5, 45.2] in women and 20.6 % [16.0, 26.0] in men for chronic knee pain. This survey revealed the differences in the multilayer proportions of medical and exercise consultation use for low back and knee pain in the cardiovascular mass screening, suggesting exercise consultation was less often provided compared to medical consultation.

PurposeEvidence regarding the dose–response curve shapes of physical activity (PA) and sedentary time (ST) in older adults with functional disability (FD) is extremely limited. Moreover, these associations may differ depending on with/without frailty. We examined the dose–response associations between moderate-to-vigorous PA (MVPA) and ST with FD among older adults with/without frailty.MethodsWe included 7,480 initially nondisabled adults (3,795 men and 3,685 women) aged 65–84 years in Ota City, Tokyo, Japan. MVPA and ST were evaluated using the International Physical Activity Questionnaire-Short Form. FD was prospectively identified using a nationally unified database of the long-term care insurance system. Frailty was determined using Check-List 15, validated against Fried’s frailty criteria. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and ST for FD were calculated, and dose–response curves were examined using restricted cubic splines.ResultsDuring 3.6 years of follow-up, 1,001 (13.4%) participants had FD. Among all participants, compared with no MVPA, the HRs for FD reduced linearly up to approximately 2000 metabolic equivalents (METs)■min/week of MVPA, and the lowest HR (HR: 0.61, 95% CI: 0.51–0.74) was reached at around 3,000–4,000 METs■min/week. Although the shape of this association was consistent regardless of with/without frailty, the magnitude of the association tended to be stronger in frail older adults than in non-frail older adults. Compared with those for the median (300 min/day) of ST, the HRs for FD increased linearly as ST reached approximately 600 min/day or more, independent of MVPA, with a maximum HR of 1.31 (95% CI: 1.01–1.71) for 1,080 min/day among all participants. This association was more pronounced among non-frail older adults but not statistically significant among frail older adults.ConclusionHigher MVPA levels consistently reduced the incidence of FD regardless of frailty in a significant inverse nonlinear dose–response manner. A significant positive nonlinear dose–response association between ST and FD risk was identified among non-frail older adults but not among frail older adults. Increasing MVPA and reducing prolonged ST are important for preventing FD among non-frail older adults. However, reducing ST alone may be insufficient; increasing MVPA, even if by only small increments, is highly recommended for frail older adults.

Abstract Objective: The consumption of various foods is internationally recommended in healthy diet although the association between dietary variety and incident dementia is unknown. We aimed to examine the association between dietary variety and the incidence of disabling dementia in older Japanese adults. Design: We conducted a prospective cohort study. Dietary variety was assessed based on the Dietary Variety Score (DVS). DVS was assessed by counting the number of ten food components (meat, fish/shellfish, eggs, milk, soyabean products, green/yellow vegetables, potatoes, fruit, seaweed and fats/oils) that were consumed almost daily using a FFQ. Participants were categorised into low (0–2 points), middle (3–4 points) and high (5–10 points) groups based on the DVS. Data on newly diagnosed disabling dementia were retrieved from the public long-term care insurance database. Cox proportional hazards regression was used to estimate hazard ratios (HR) with 95 % CI. Setting: Yabu cohort study, Japan. Participants: A total of 4972 community-dwelling adults aged 65 years or older. Results: During the median follow-up of 6·8 years, 884 participants were newly diagnosed with disabling dementia. After adjusting for confounders, the multivariable-adjusted HR for incident disabling dementia was 0·82 (95 % CI, 0·69, 0·97) for participants in the highest DVS category compared with those in the lowest DVS category (P for trend = 0·019). Conclusions: A higher dietary variety is associated with a reduced risk of disabling dementia in older Japanese adults. These results have potential implications for the development of effective public nutritional approaches to prevent dementia in older adults.

Background: This 3.6-year prospective study examined combined impacts of physical activity, dietary variety, and social interaction on incident disability and estimated population-attributable fraction for disability reduction in older adults. Methods: Participants were 7,822 initially non-disabled residents (3,966 men and 3,856 women) aged 65–84 years of Ota City, Tokyo, Japan. Sufficiency of moderate-to-vigorous-intensity physical activity (MVPA) ≥150 min/week, dietary variety score (DVS) ≥3 (median), and social interaction (face-to-face and/or non-face-to-face) ≥1 time/week was assessed using self-administered questionnaires. Disability incidence was prospectively identified using the long-term care insurance system’s nationally unified database. Results: During a follow-up of 3.6 years, 1,046 (13.4%) individuals had disabilities. Independent multivariate-hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA, DVS, and social interaction sufficiency for incident disability were 0.68 (95% CI, 0.59–0.78), 0.87 (95% CI, 0.77–0.99), and 0.90 (95% CI, 0.79–1.03), respectively. Incident disability HRs gradually reduced with increased frequency of satisfying these behaviors (any one: HR 0.82; 95% CI, 0.65–1.03; any two: HR 0.65; 95% CI, 0.52–0.82; and all three behaviors: HR 0.54; 95% CI, 0.43–0.69), in an inverse dose-response manner (P < 0.001 for trend). Population-attributable fraction for disability reduction in satisfying any one, any two, and all three behaviors were 4.0% (95% CI, −0.2 to 7.9%), 9.6% (95% CI, 4.8–14.1%), and 16.0% (95% CI, 8.7–22.8%), respectively. Conclusion: Combining physical activity, dietary variety, and social interaction substantially enhances the impacts on preventing disability among older adults, with evidence of an inverse dose-response manner. Improving insufficient behavior elements through individual habits and preexisting social group activities may be effective in preventing disability in the community.

This prospective study examined the associations of dog/cat ownership with incident disabling dementia using propensity score matching based on the physical, social, and psychological characteristics of dog and cat owners. We also examined associations of the interaction between dog/cat ownership and exercise habit and social isolation with dementia. Overall, 11,194 older adults selected using stratified and random sampling strategies in 2016 were analyzed. Dog/cat ownership was defined as “current” or “past and never”. Disabling dementia was defined according to physicians’ rating in the long-term care insurance system in Japan during the approximately 4-year follow-up period. Statistical analysis was weighted by the inverse of the propensity score in the generalized estimating equation after adjusting for follow-up period. Current dog owners (8.6 %) had an odds ratio (OR) of 0.60 (95 %CI: 0.37–0.977) of having disabling dementia compared to past and never owners. For cat ownership, the corresponding OR was 0.98 (95 %CI: 0.62–1.55). Current dog owners with a regular exercise habit had an OR of 0.37 (0.20–0.68) compared to past and never dog owners with no exercise habit. Further, current dog owners with no social isolation had an OR of 0.41 (0.23–0.73) compared to past and never dog owners with social isolation. Dog ownership had a suppressive effect on incident disabling dementia after adjusting for background factors over a 4-year follow-up period. Specifically, dog owners with an exercise habit and no social isolation had a significantly lower risk of disabling dementia.

Abstract Background Few studies have examined the state of oral function in older adults with sarcopenia. We assessed the oral functions of community‐dwelling older adults with sarcopenia from multiple perspectives to clarify their potentially low oral function. Methods A total of 1517 (86.2%; 990 women, 527 men; mean age 76.1 ± 7.6 years) participants were included in this study. Grip strength, gait speed and skeletal muscle mass index were assessed, and sarcopenia was evaluated according to the criteria of the Asian Working Group for Sarcopenia 2019. The degree of tongue coating, oral moisture, occlusal force, tongue–lip motor function, tongue pressure, masticatory function and swallowing function were assessed. The criteria for oral hypofunction (a disease that is a combination of multiple low oral functions) were used to assess oral function. Statistical analyses were performed using Kolmogorov–Smirnov test, unpaired t‐test, Mann–Whitney U test, χ2 test, and univariate and multivariable logistic regression analyses, with each oral function as the dependent variable and sarcopenia as one of the independent variables. The significance level was set at P

Abstract Aims Evidence on the risk factors for incident heart failure in Asia has been limited. We sought to identify the risk factors for pre‐heart failure or symptomatic heart failure, based on N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), in the Japanese general population. Methods We performed a retrospective cohort study based on the Circulatory Risk in Communities Study involving 5335 Japanese individuals whose NT‐proBNP levels were measured between 2010 and 2015. Of these, 2768 people aged between 30 and 69 years who undertook annual cardiovascular risk surveys at least once between 1990 and 2000 were retrospectively eligible to be participants in this study. We performed multivariable logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pre‐heart failure or symptomatic heart failure defined as NT‐proBNP >400 pg/mL or as having a diagnosis of heart failure and taking medication for heart failure for several cardiovascular risk factors (body mass index, blood pressure, diabetes mellitus, total cholesterol, triglyceride, smoking status, drinking status). Results We identified 85 cases of heart failure. The multivariable ORs (95% CIs) were 5.70 (2.70–12.0) for body mass index of 27–29.9 kg/m2 and 5.91 (2.19–16.0) for ≥30 kg/m2 compared with 21–22.9 kg/m2; 2.49(1.01–6.13) for systolic blood pressure of ≥160 mmHg vs.

Background: To clarify the association between psychosocial problems and frailty in the areas affected by the Great East Japan Earthquake, and to develop strategies for preventive long-term care in the community, we launched the Kesennuma Study in 2019. This report describes the study design and the participants’ profiles at baseline. Methods: The prospective study comprised 9,754 people (4,548 men and 5,206 women) randomly selected from community-dwelling independent adults aged 65 to 84 who were living in Kesennuma City, Miyagi. The baseline survey was conducted in October 2019. It included information on general health, socio-economic status, frailty, lifestyle, psychological factors (eg, personality, depressive moods), and social factors (eg, social isolation, social capital). A follow-up questionnaire survey is planned. Mortality, incident disability, and long-term care insurance certifications will also be collected. Results: A total of 8,150 questionnaires were returned (83.6% response rate), and 7,845 were included in the analysis (80.4%; mean age 73.6 [standard deviation, 5.5] years; 44.7% male). About 23.5% were considered frail. Regarding psychological and social functions, 42.7% had depressive moods, 29.1% were socially isolated, and only 37.0% participated in social activities at least once a month. However, 82.5% trusted their neighbors. Conclusion: While local ties were strong, low social activity and poor mental health were revealed as issues in the affected area. Focusing on the association between psychological and social factors and frailty, we aim to delay the need for long-term care for as long as possible, through exercise, nutrition, social participation, and improvement of mental health.

Healthy behaviours reduce the risk of incident disability; however, their components require further consideration. Specifically, little evidence exists on healthy behaviours that comprise modifiable factors, including social aspects, and their effects on those who do not engage in them. This study aimed to examine the association between engaging in healthy behaviours with modifiable factors and incident disability among community-dwelling older adults; as well as identify factors associated with nonengagement in healthy behaviours. We analysed data obtained from 1357 older adults aged 65 years and more without disabilities at baseline. The outcome was incident disability, which was defined based on the long-term care insurance certification in Japan. This study included regular exercise (≥1 day/week), favourable eating habits (≥4 dietary variety score), and social participation (engaging in two or more social activities) as components of healthy behaviours. We used the Cox proportional hazards model to calculate hazard ratios (HR) for incident disabilities. The proportion of those who satisfied all healthy behaviours was 21 %. During the follow-up period (median: 6.3 years), 282 incident disabilities were confirmed. Compared to those who engaged in one healthy behaviour, those who satisfied all healthy behaviours showed a 31 % (95 % confidence interval: 0.48, 0.98) lower HR of incident disability after adjusting for covariates. Current smoking and depressive mood were associated with non-engagement in healthy behaviours. This study found that having physically and socially active lifestyles and favourable eating habits are effective in reducing the risk of incident disability. Meanwhile, several older adults lack the components of a healthy lifestyle. Approaches that focus on multiple healthy behaviours are necessary to enhance the benefits of healthy lifestyles.

Abstract Background Sarcopenia‐related parameters may have differential impacts on health‐related outcomes in older adults. We examined dose–response relationships of body composition, muscle strength, and physical performance with incident disability and mortality. Methods This prospective study included 1765 Japanese residents (862 men; 903 women) aged ≥65 years who participated in health check‐ups. Outcomes were incident disability and all‐cause mortality. Fat mass index (FMI) and skeletal muscle mass index (SMI), determined using segmental multi‐frequency bioelectrical impedance analysis, handgrip strength (HGS), and usual gait speed (UGS) were measured. We determined multivariate‐adjusted hazard ratios (HRs) for disability and mortality relative to sex‐specific reference values (FMI: medians; SMI: 7.0 kg/m2 for men and 5.7 kg/m2 for women; HGS: 28 kg for men and 18 kg for women; or UGS: 1.0 m/s for both sexes). Association shapes were examined using restricted cubic splines or fractional polynomial functions. Results The median follow‐up was 5.3 years; 107 (12.7%) men and 123 (14.2%) women developed disability, and 101 (11.7%) men and 56 (6.2%) women died. FMI did not impact any outcome in men and disability in women, while an FMI ≤ 7.3 kg/m2 (median) was significantly associated with higher mortality risk in women, compared with median FMI. SMI did not impact disability in either sex and mortality in women, but showed a significant inverse dose–response relationship with mortality risk in men [HRs (95% confidence intervals) of minimum and maximum values compared with the reference value: 2.18 (1.07–4.46) and 0.43 (0.20–0.93), respectively], independent of HGS and UGS. HGS and UGS showed a significant inverse dose–response relationship with disability in both sexes [HGS: 1.71 (1.00–2.91) and 0.31 (0.09–0.99), respectively, in men, 2.42 (1.18–4.96) and 0.41 (0.20–0.85), respectively, in women; UGS: 2.14 (1.23–3.74) and 0.23 (0.08–0.67), respectively, in men, 3.26 (2.07–5.14) and 0.11 (0.05–0.26), respectively, in women] and mortality in women [HGS: 6.84 (2.84–16.47) and 0.06 (0.02–0.21), respectively; UGS: 2.67 (1.14–6.27) and 0.30 (0.11–0.85), respectively], independent of body composition, but did not impact mortality in men. Conclusions Disability risk was more dependent on muscle strength and physical performance in both sexes. Mortality risk in men was more dependent on muscle mass, and mortality risk in women was influenced by lower fat mass along with muscle strength and physical performance. Although improving muscle strength and physical performance should be the first target for health promotion, it is also necessary to pay attention to body composition to extend life expectancy in older adults.

This study examined the differences in medical and long-term care costs over 18 months between pet owners and non-owners among community-dwelling older Japanese. Pet ownership data were collected from 460 community-dwelling adults age 65 years and older. These data were matched with data from the National Health Insurance, health insurance for older people, and Long-Term Care Insurance beneficiaries for 17 months back from the survey on pet ownership. Pet-ownership group-specific trajectories in monthly medical and long-term care costs were modeled by a generalized estimating equation. Among pet owners (n = 96, 20.9%) and non-pet owners (n = 364, 79.1%) there were no significant differences in baseline demographic or health characteristics including chronic disease and self-reported long-term care level. At baseline, pet owners had estimated monthly medical costs of ¥48,054 (SE = 0.11; $418), compared to ¥42,260 (SE = 0.06; $367) for non-pet owners. The monthly medical costs did not differ significantly between the two groups during the 18-month follow-up period. At baseline, estimated monthly long-term care costs of pet owners and non-pet owners were ¥676 (SE = 0.75; $6) and ¥1,420 (SE = 0.52; $12), respectively. During the follow-up period, the non-pet owner to owner ratio of monthly long-term care costs was 1.2 at minimum and 2.3 at maximum. This study showed that monthly long-term care costs for pet owners were approximately half those of non-pet owners. Pet owners might use long-term care services less frequently, or use lighter care services.

BackgroundNutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.MethodIn a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.Clinical trial registration[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

Background: The association between overweight and chronic musculoskeletal pain may vary by anatomical site and be modified by hypertension status. This study examined the associations between overweight and low back and knee pains and their effect modification by hypertension status. Methods: We conducted a community-based cross-sectional study involving 2,845 adults (1,080 men and 1,765 women) aged 40–89 years. Chronic knee pain (CKP) and low back pain (CLBP) lasting more than 3 months were categorized into more or less severe pain. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between overweight and more or less severe CKP and CLBP were determined using logistic regression and stratified by hypertension status. Adjustment variables were age, sex, area, hypertension, smoking and drinking status, inactivity, job category, mental stress, depression, and overall CKP or CLBP. Results: Overall, 288 (10.1%) and 631 (22.2%) adults had more and less severe CKP, respectively, and 284 (10.0%) and 830 (29.2%) had more and less severe CLBP, respectively. Overweight was associated with overall CKP and more or less severe CKP, regardless of hypertension status. Overweight was not associated with overall CLBP; its association was more pronounced for more severe CLBP. The association between overweight and more severe CLBP was evident among non-hypertensives (multivariable OR 1.72; 95% CI, 1.09–2.71); however, that between overweight and less severe CLBP was not evident (multivariable OR 1.07; 95% CI, 0.73–1.56). Conclusions: As hypertension may attenuate the association between overweight and CLBP, we should consider hypertension status for proper management of CLBP among overweight individuals.

Abstract Aims Although aging is strongly associated with both heart failure and a decline in gait speed, a definition of slowness incorporating an age‐related decline has yet to be developed. We aimed to define an event‐driven cut‐off for the relative decline in gait speed against age‐adjusted reference values derived from the general population and evaluate its prognostic implications. Methods and results Standardized gait speed (SGS) was defined as the median gait speed stratified by age, sex, and height in 3777 elderly (age ≥ 65 years) individuals without a history of cardiovascular diseases (Tokyo Metropolitan Institute of Gerontology‐Longitudinal Interdisciplinary Study on Aging: general population cohort). The mortality event‐driven optimal cut‐off of the SGS ratio (actual gait speed divided by the respective SGS) was defined using FRAGILE‐HF cohort data and externally validated using Kitasato cohort data, comprising 1301 and 1247 hospitalized elderly patients with heart failure, respectively. Using FRAGILE‐HF data, the optimal SGS ratio cut‐off was determined as 0.527. In the Kitasato cohort, SGS ratio

Abstract Background Generalized loss of skeletal muscle mass (SMM) may modulate or otherwise affect the loss of masseter muscle mass and be responsible for low masseter muscle performance and strength (i.e., low oral function). Moreover, dentition status can affect oral function independent of the muscle state. This cross-sectional study aimed to simultaneously investigate the relationships among whole-body SMM, masseter muscle mass, oral function (masseter muscle performance and strength), and dentition status in 1349 Japanese adults (mean age = 73.6 years). Methods We determined the estimated masseter muscle mass (e-MMM) based on morphological measurements of the masseter muscle. Masseter muscle performance was assessed via masticatory performance evaluation scores using gum, and strength was assessed as the maximal occlusal force. Dentition status was assessed as the number of functional teeth. SMM was measured by bioelectrical impedance analysis. Structural equation modeling stratified by sex was employed to investigate associations among SMM, e-MMM, gum score, occlusal force, and number of functional teeth. Results The direct path from SMM to e-MMM was statistically significant, as was the direct path from e-MMM to oral function (gum score and maximum occlusal force) for both sexes. We additionally confirmed that SMM indirectly affected gum score and maximum occlusal force via e-MMM (men; standardized coefficient [95% CI] = 3.64 [1.31 to 5.96] for maximum occlusal force and 0.01 [0.01 to 0.02] for gum score, women; 2.01 [0.38 to 3.81] for maximum occlusal force and 0.01 [0.002 to 0.01] for gum score). The number of functional teeth had direct effects on e-MMM, gum score, and maximum occlusal force. Conclusions Low SMM was significantly indirectly associated with poor oral function through a low masseter muscle mass, and dentition status was independently associated with oral function.

Abstract Tocopherols, strong antioxidants, may be useful in preventing dementia, but the epidemiological evidence is insufficient. We performed a community-based follow-up study of Japanese, the Circulatory Risk in Community Study, involving 3739 people aged 40–64 years at baseline (1985–1999). Incident disabling dementia was followed up from 1999 through 2020. For subtype analysis, we classified disabling dementia into that with and that without a history of stroke. Dietary intake of tocopherols (total, α, β, γ, and δ) were estimated using 24-h recall surveys. During a median follow-up of 19.7 years, 670 cases of disabling dementia developed. Total tocopherol intake was inversely associated with risk of disabling dementia with multivariable hazard ratios (95% confidence intervals) of 0.79 (0.63–1.00) for the highest versus lowest quartiles of total tocopherol intake (P for trend = 0.05). However, the association was strengthened when further adjusted for α-linolenic acid intake (Spearman correlation with total tocopherol intake = 0.93), with multivariable hazard ratios of 0.50 (0.34–0.74) (P for trend = 0.001) but was weakened and nonsignificant when further adjusted for linoleic acid intake (Spearman correlation with total tocopherol intake = 0.92), with multivariable hazard ratios of 0.69 (0.47–1.01) (P for trend = 0.05). Similar but nonsignificant inverse associations were observed for α-, γ-, and δ-tocopherols but not for β-tocopherol. These results were similar regardless of the presence of a history of stroke. Dietary tocopherol intake was inversely associated with risk of disabling dementia, but its independent effect was uncertain owing to a high intercorrelation of α-linolenic linoleic acids with total tocopherol intake. Even with such confounding, a diet high in tocopherols may help prevent the onset of dementia.

Background: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). Methods: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40–74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. Results: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48–0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52–0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56–1.08), p for trend = 0.036, and 1.24 (0.89–1.75), p for trend = 0.270. Conclusions: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

Background: The frequency of laughter has been associated with cardiovascular disease and related biomarkers, but no previous studies have examined association between laughter and changes in blood pressure levels. We sought to identify temporal relationships between frequency of laughter in daily life and systolic and diastolic blood pressure changes in participants from 2010 through 2014. Methods: Participants were 554 men and 887 women aged 40–74 years who answered self-administered questionnaire quantifying frequency of laughter at baseline. We measured participant blood pressure levels twice using automated sphygmomanometers for each year from 2010 to 2014. The associations between laughter and changes in blood pressure over time were analyzed using linear mixed-effect models. Results: There was no significant difference in blood pressure according to frequency of laughter at baseline in either sex. Men with frequency of laughter 1 to 3 per month or almost never had significantly increased systolic and diastolic blood pressure levels over the 4-year period (time-dependent difference: 0.96 mm Hg (95% confidence interval [CI], −0.2 to 1.8; P = 0.05). Changes in blood pressure associated with infrequent laughter (ie, 1 to 3 per month or almost never) were evident in men without antihypertensive medication use over 4 years (0.94 mm Hg; 95% CI, −0.2 to 2.0; P = 0.09) and men who were current drinkers at baseline (1.29 mm Hg; 95% CI, −0.1 to 2.3; P = 0.04). No significant difference was found between frequency of laughter and systolic (0.23 mm Hg; 95% CI, −1.0 to 1.5; P = 0.72) and diastolic (−0.07 mm Hg; 95% CI, −0.8 to 0.7; P = 0.86) blood pressure changes in women. Conclusions: Infrequent laughter was associated with long-term blood pressure increment among middle-aged men.

Abstract Background There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community‐dwelling older adults. Methods We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check‐ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi‐frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all‐cause mortality and incident disability. Results The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia‐related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P‐values

Background/purpose: Color-changeable chewing gum is used for the evaluation of masticatory performance. However, it is currently unclear whether colorimetric and visual assessment methods yield consistent results. This study aimed to clarify the consistency between colorimetric and visual methods used for the evaluation of color changes in color-changeable chewing gum. Materials and methods: The sample comprised 644 older persons (mean age, 75.4 ± 6.4 years). The chewing gum was masticated 60 times at the participant's own chewing rate and then expectorated. The color of the chewing gum was evaluated with the ΔE values and a∗ values, measured using a colorimeter, and the 10 Color Shades (10CSh) and 5 Color Scales (5CSc), using visual evaluation. Spearman's correlation analysis was performed to examine the correlation between the results obtained by the four methods. The significance level was set at α = 0.05. Results: The ΔE values, a∗ values, 10CSh scores, and 5CSc scores were all significantly correlated. The highest correlation coefficient (0.979) was between the ΔE values and a∗ values. The lowest correlation coefficient (0.847) was between the a∗ values and 5CSc scores. Decreased masticatory performance was observed with increased age. Conclusion: Significant correlations were found for all four methods used in the assessment of masticatory performance with color-changeable chewing gum. While visually based assessments are valid, colorimetric methods are more sensitive to smaller changes in masticatory performance.

Abstract Background Diet is a modifiable factor affecting sarcopenia, and accumulating evidence links dietary factors to muscle mass, strength, and function in older adults. However, few studies have examined the association of dietary patterns with sarcopenia. This study examined the association of dietary patterns derived by reduced-rank regression (RRR) with sarcopenia and its components in community-dwelling older Japanese. Methods We conducted a cross-sectional study of 1606 community-dwelling adults aged 65 years or older. Dietary intake was assessed by a validated, self-administered diet history questionnaire. Nutrient-derived dietary patterns were identified by using RRR, with sarcopenia-related nutrients (protein, vitamin D, vitamin C, vitamin E, folate, vitamin K, magnesium, iron, and calcium intakes) as response variables. Sarcopenia was defined by using the algorithm of the Asian Working Group for Sarcopenia 2019. Multivariate regression and logistic regression were used to examine the association of dietary patterns with sarcopenia and its components. Results The first RRR dietary pattern was characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, and fruit and a low intake of rice and was associated with decreased prevalence of sarcopenia: the multivariable-adjusted odds ratio of sarcopenia was 0.57 (95% confidence interval, 0.34–0.94; p for trend=0.022) in the highest versus the lowest tertile of dietary pattern. This dietary pattern was also significantly positively associated with usual gait speed (β: 0.02, p=0.024). Conclusions A dietary pattern characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, and fruits and low rice intake was inversely associated with sarcopenia in community-dwelling older Japanese.

Background: It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods: We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results: The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions: We expect to provide scientific evidence on the effectiveness of health counselling.

Objectives This study examined the association between dog and cat ownership, the onset of disability and all-cause mortality in an older population. Dog and cat owners take more regular exercise and have closer social relationships than non-owners. We further assess the beneficial effects of these moderating variables on the onset of disability and mortality. Methods Dog and cat ownership data were collected from 11233 community-dwelling adults age 65 years and older. These data were matched with data about the onset of disability held by the Japanese long-term care insurance system. Local registry data were used to ascertain all-cause mortality. Results During the approximately 3.5 year follow-up period, 17.1% of the sample suffered onset of disability, and 5.2% died. Logistic regression analysis indicated that, compared with a reference group of those who had never owned a dog (odds ratio fixed at 1.0), older adults who were currently dog owners had a significantly lower odds ratio of onset of disability (OR = 0.54 95% CI: 0.37–0.79). Our results further show that regular exercise interacts with dog ownership to reduce the risk of disability. The association of dog and/or cat ownership with all-cause mortality was not statistically significant. Conclusions Dog ownership appears to protect against incident disability among older Japanese adults. Additional benefits are gained from ownership combined with regular exercise. Daily dog care may have an important role to play in health promotion and successful aging.

Background: Sex- and age-specific impacts of cardiovascular risk factors on the development of dementia have not been well evaluated. We investigated these impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus on the risk of disabling dementia. Methods: The study participants were 25,029 (10,134 men and 14,895 women) Japanese aged 40–74 years without disabling dementia at baseline (2008–2013). They were assessed on smoking status (non-current or current), overweight/obesity (body mass index ≥25 kg/m2 and ≥30 kg/m2, respectively), hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or any antihypertensive medication use), and diabetes mellitus (a fasting serum glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, hemoglobin A1c ≥6.5% by the National Glycohemoglobin Standardization Program or glucose-lowering medication use) at baseline. Disabling dementia was identified as the level of care required ≥1 and cognitive disability grade ≥IIa according to the National Long-term Care Insurance Database. We used a Cox proportional regression model to estimate hazard ratios and 95% confidence intervals (95% CIs) of disabling dementia according to the cardiovascular risk factors and calculated the population attributable fractions (PAFs). Results: During a median follow-up of 9.1 years, 1,322 (606 men and 716 women) developed disabling dementia. Current smoking and hypertension were associated with a higher risk of disabling dementia in both sexes, whereas overweight or obesity was not associated with the risk in either sex. Diabetes mellitus was associated with a higher risk only in women (p for sex interaction = 0.04). The significant PAFs were 13% for smoking and 14% for hypertension in men and 3% for smoking, 12% for hypertension, and 5% for diabetes mellitus in women. The total PAFs of the significant risk factors were 28% in men and 20% in women. When stratified by age, hypertension in midlife (40–64 years) was associated with the increased risk in men, while diabetes mellitus in later-life (65–74 years) was so in women. Conclusions: A substantial burden of disabling dementia was attributable to smoking, and hypertension in both sexes and diabetes mellitus in women, which may require the management of these cardiovascular risk factors to prevent dementia.

Summary: Evidence linking the gut-brain axis to Alzheimer’s disease (AD) is accumulating, but the characteristics of causally important microbes are poorly understood. We perform a fecal microbiome analysis in healthy subjects and those with mild cognitive impairment (MCI) and AD. We find that Faecalibacterium prausnitzii (F. prausnitzii) correlates with cognitive scores and decreases in the MCI group compared with the healthy group. Two isolated strains from the healthy group, live Fp360 and pasteurized Fp14, improve cognitive impairment in an AD mouse model. Whole-genome comparison of isolated strains reveals specific orthologs that are found only in the effective strains and are more abundant in the healthy group compared with the MCI group. Metabolome and RNA sequencing analyses of mouse brains provides mechanistic insights into the relationship between the efficacy of pasteurized Fp14, oxidative stress, and mitochondrial function. We conclude that F. prausnitzii strains with these specific orthologs are candidates for gut microbiome-based intervention in Alzheimer's-type dementia.

Background: Although an elevated systolic blood pressure (SBP) is associated with cognitive dysfunction, BP may decrease with advanced cognitive dysfunction; therefore, we attempted to identify the turning point in the relationship between cognitive function and SBP in elderly subjects. Methods: In pooled datasets of general populations and outpatient clinics (age>65 years), in which the risk of frailty or cognitive dysfunction was assessed (N = 4076), the relationship between SBP and the Mini Mental State Examination (MMSE) score was examined. Results: Mean age was 72.5 ± 6.2 years (male 45.1%), and SBP was 133.0 ± 19.5 mmHg. In an analysis of locally weighted scatter plot smoothing, the relationship between SBP and MMSE scores changed at an MMSE score of 24 points. In subjects with preserved cognitive function (MMSE ≥24 points), MMSE scores decreased with increases in SBP (B = −0.047 per 10 mmHg increase, P = 0.002) after adjustments for age, sex, body mass index, alcohol habit, smoking status, diabetes, a history of stroke, and the geriatric nutritional index; however, in subjects with reduced cognitive function (MMSE

Introduction: Chronic low back pain (CLBP), defined as low back pain persisting for at least 3 months, leads to limitations in the activities of daily living and decreased quality of life. Individualized self-exercise education could be a preferable treatment option, especially in community-dwelling people with CLBP. Previous studies, however, did not directly compare the effects of therapist-led self-exercise education and material-only education, and there are only a few studies investigating the effects of low-dose (comprising a few sessions) self-exercise education on CLBP. We present a protocol of community-based, randomized study to evaluate the effects of low-dose (comprising a few sessions), therapist-led self-exercise education on CLBP. Methods: Forty-eight participants with CLBP (men and women, aged 40-74 years) will be allocated to therapeutic self-exercise education programs, either a therapist-led group (2-week therapist's consultation and material use) or material-only group (material use only), in a randomized controlled trial. Pain intensity (NRS, numeric rating scale), pain disability (RDQ, Roland-Morris disability questionnaire), pain self-efficacy (PSEQ, pain self-efficacy questionnaire), and quality of life score (EQ-5D, European quality of life-5 dimensions) will be measured at baseline and at 4, 12, and 24 weeks. We will apply a repeated-measures design with mixed-effect models to estimate group differences from the baseline. Ethics/Trial registration number: The protocol was approved by the Ethics Committees of the Osaka Center for Cancer and Cardiovascular Disease Prevention and Osaka University. The trial registration number is registered on the University Hospital Medical Information Network (UMIN000024537).

Background: Although meals that combine a staple food, main dish, and side dish (balanced meals) are recommended in Japan, the health effects of such meals are unclear. We investigated the association of frequency of eating balanced meals with frailty among community-dwelling older Japanese. Methods: We analyzed data from 912 persons aged 65 years or older who participated in the Hatoyama Cohort Study or Kusatsu Longitudinal Study. The frequency of eating two or more balanced meals daily was self-reported as ≤1 day/week, 2 or 3 days/week, 4 or 5 days/week, and daily. Frailty was defined as the presence of at least three, and pre-frailty as the presence of one or two, of the following criteria: weight loss, muscle weakness, exhaustion, slowness, and low physical activity. Adjusted logistic regression was used to study associations of frequency of balanced-meal consumption with frailty (prefrailty and frailty combined) and frailty criteria. Results: Participants reporting a frequency of balanced-meal consumption of ≤2 or 3 days/week had a higher prevalence of frailty (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.21–2.64) than did those reporting a frequency of daily. Lower frequency of balanced-meal consumption was also associated with higher prevalences of weight loss (OR, 4.10; 95% CI, 1.90–8.85), exhaustion (OR, 6.35; 95% CI, 2.49–16.17), and low physical activity (OR, 1.92; 95% CI, 1.22–3.01). Conclusions: Our findings suggest that more frequent twice daily consumption of meals with a staple food, main dish, and side dish decreases the risks of prefrailty and frailty.

The Circulatory Risk in Communities Study (CIRCS) is an ongoing community-based epidemiological study of lifestyle-related disease involving dynamic prospective cohorts of approximately 12,000 adults from five communities of Japan: Ikawa, Ishizawa and Kita-Utetsu (Akita Prefecture), Minami-Takayasu (Osaka Prefecture), Noichi (Kochi Prefecture), and Kyowa (Ibaraki Prefecture). One of the most notable features of CIRCS is that it is not only an observational cohort study to identify risk factors for cardiovascular diseases (CVD), such as stroke, coronary heart disease, and sudden cardiac death, but it also involves prevention programs for CVD. Using basic, clinical, epidemiological, and statistical techniques, CIRCS has clarified characteristics of CVD and the related risk factors to develop specific methodologies towards CVD prevention in Japanese middle-aged or older adults for more than half a century.

Background: Preventing and reducing frailty is an important challenge for Japan in the next decade, especially in metropolitan areas. We launched a community-wide intervention trial (the Ota Genki Senior Project) in 2016 to develop effective community-based strategies for frailty prevention in metropolitan areas. This report describes the study design and baseline survey. Methods: This study is a community-wide intervention trial that integrates participatory action research into a cluster non-randomized controlled trial for adults aged 65 years or older living in Ota City, Tokyo. We allocated 3 of 18 districts to an intervention group and the other 15 to a control group. Using a mailed self-administered questionnaire, we conducted a baseline survey of 15,500 residents (8,000 and 7,500 in the intervention and control groups, respectively) from July through August 2016. In addition to socioeconomic status and lifestyle variables, we assessed frailty status (primary outcome) and physical, nutritional, and psychosocial variables (secondary outcomes). Based on the baseline findings, an intervention to improve outcomes will be implemented as participatory action research. Follow-up surveys will be conducted in the same manner as the baseline survey. Results: A total of 11,925 questionnaires were returned (76.9% response rate; 6,105 [76.3%] and 5,820 [77.6%] in the intervention and control groups, respectively), and 11,701 were included in the analysis (mean age, 74.3 [standard deviation, 5.5] years; 48.5% were men). Conclusions: This study is expected to contribute to development of a prototype of a community-wide frailty prevention strategy, especially in metropolitan areas in Japan. Trial registration: UMIN Clinical Trials Registry (UMIN000026515).

Background Evidence on the associations of carotid intima‐media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population. Methods and Results Maximum intima‐media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima‐media thicknesses of the common carotid artery were 1.97 (1.26–3.06) for total stroke, 1.52 (0.67–3.41) for hemorrhagic stroke, 2.45 (1.41–4.27) for ischemic stroke, 3.60 (1.64–7.91) for lacunar infarction, 1.53 (0.69–3.41) for nonlacunar cerebral infarction, 2.68 (1.24–5.76) for coronary artery disease, and 2.11 (1.44–3.12) for cardiovascular disease (similar results were found for maximum intima‐media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09–2.30) for total stroke, 1.25 (0.58–2.70) for hemorrhagic stroke, 1.74 (1.13–2.67) for ischemic stroke, 1.84 (1.03–3.19) for lacunar infarction, 1.58 (0.80–3.11) for nonlacunar cerebral infarction, 2.11 (1.20–3.70) for coronary artery disease, and 1.71 (1.25–2.35) for cardiovascular disease. Conclusions Maximum intima‐media thicknesses of the common carotid artery, maximum intima‐media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.

Abstract Objective We aimed to investigate associations between cardiovascular reactivity to acute stress and sickness absence among Japanese male and female workers, in a prospective study. Methods Among healthy employed Japanese workers who underwent mental health checks between 2006 and 2009, data of 111 participants were analyzed. Changes in blood pressure, pulse rate, peripheral blood flow (PBF), and heart rate variability (HRV) (high frequency [HF] and low frequency [LF]) were calculated using differences between the two tasks, mirror drawing stress [MDS] and a maze task, and the postperiod value. Sickness absence through March 2010 was followed up by mail survey (average follow‐up 2.3 years). Logistic regression analysis was used, adjusting for lifestyle factors. Results Among 12 participants who took sickness absences, eight were owing to mental problems. Changes in the LF during the MDS and maze tasks and LF‐to‐HF ratio during the MDS task were positively associated with all sickness absences (odds ratio [OR], 95% confidence interval [CI]: 2.09, 1.03–4.22; 2.04, 1.09–3.82; and 3.10, 1.46–6.58, respectively). Changes in PBF during the MDS task were also associated with increased risk of sickness absence (OR, 95% CI: 2.53, 1.10–5.81). Conclusion Cardiovascular reactivity to acute stress should be considered at workers' health checks.

Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with memory function, and elderly people with high protein intake have a low risk of mild cognitive impairment. Although the beneficial roles of protein nutrition in maintaining brain function in aged people are well demonstrated, little is known about the mechanism by which dietary intake of protein affects memory and brain conditions. We fed aged mice a low protein diet (LPD) for 2 months, which caused behavioral abnormalities, and examined the nutritional effect of essential amino acid administration under LPD conditions. The passive avoidance test revealed that LPD mice demonstrated learning and memory impairment. Similarly, the LPD mice showed agitation and hyperactive behavior in the elevated plus maze test. Moreover, LPD mice exhibited decreased concentrations of gamma-aminobutyric acid (GABA), glutamate, glycine, dopamine, norepinephrine, serotonin and aspartate in the brain. Interestingly, oral administration of seven essential amino acids (EAAs; valine, leucine, isoleucine, lysine, phenylalanine, histidine, and tryptophan) to LPD mice, which can be a source of neurotransmitters, reversed those behavioral changes. The oral administration of EAAs restored the brain concentration of glutamate, which is involved in learning and memory ability and may be associated with the observed behavioral changes. Although the details of the link between decreased amino acid and neurotransmitter concentrations and behavioral abnormalities must be examined in future studies, these findings suggest the importance of dietary protein and essential amino acids for maintaining brain function.

The Japanese government encourages older adults to participate in annual health checkups designed to detect lifestyle diseases such as hypertension, diabetes, and dyslipidemia. However, individuals who are already being treated for these diseases are unlikely to benefit from health checkup participation. This retrospective cohort study of older adults evaluated the associations of pharmacological treatments for these diseases with health checkup participation and identified the disease control factors among patients receiving treatments. Using medical claims data and health checkup data between September 2013 and August 2014 from 820,215 older adults aged ≥ 75 years residing in Tokyo, Japan, we examined the associations between pharmacological treatments and health checkup participation using binary logistic regression analysis. Next, patients receiving pharmacological treatments were categorized into intensive, moderate, or limited disease control based on their blood pressure, hemoglobin A1c levels, and lipid levels; multinomial logistic regression analyses were used to identify the disease control factors. The results showed that patients receiving pharmacological treatments were more likely (odds ratio: 1.374; P

Nutritional epidemiology has shown the importance of protein intake for maintaining brain function in the elderly population. Mild cognitive impairment (MCI) may be associated with malnutrition, especially protein intake. We explored blood-based biomarkers linking protein nutritional status with MCI in a multicenter study. In total, 219 individuals with MCI (79.5 ± 5.7 year) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 year) in four different cities in Japan were recruited. They were divided into the training (120 MCI and 120 CN) and validation (99 MCI and 100 CN) groups. A model involving concentrations of PFAAs and albumin to discriminate MCI from CN individuals was constructed by multivariate logistic regression analysis in the training dataset, and the performance was evaluated in the validation dataset. The concentrations of some essential amino acids and albumin were significantly lower in MCI group than CN group. An index incorporating albumin and PFAA discriminated MCI from CN participants with the AUC of 0.705 (95% CI: 0.632–0.778), and the sensitivities at specificities of 90% and 60% were 25.3% and 76.8%, respectively. No significant association with BMI or APOE status was observed. This cross-sectional study suggests that the biomarker changes in MCI group may be associated with protein nutrition.

Abstract Background Although frailty and cognitive impairment are critical risk factors for disability and mortality in the general population of older inhabitants, the prevalence and incidence of these factors in individuals treated in the specialty outpatient clinics are unknown. Methods We recently established a frailty clinic for comprehensive assessments of conditions such as frailty, sarcopenia, and cognition, and planned 3-year prospective observational study to identify the risk factors for progression of these aging-related statuses. To date, we recruited 323 patients who revealed symptoms suggestive of frailty mainly from a specialty outpatient clinic of cardiology and diabetes. Frailty status was diagnosed by the modified Cardiovascular Health Study (mCHS) criteria and some other scales. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Japanese version of the Montreal Cognitive Assessment (MoCA-J), and some other modalities. Sarcopenia was defined by the criteria of the Asian Working Group for Sarcopenia (AWGS). In this report, we outlined our frailty clinic and analyzed the background characteristics of the subjects. Results Most patients reported hypertension (78%), diabetes mellitus (57%), or dyslipidemia (63%), and cardiovascular disease and probable heart failure also had a higher prevalence. The prevalence of frailty diagnosed according to the mCHS criteria, cognitive impairment defined by MMSE (≤27) and MoCA-J (≤25), and of AWGS-defined sarcopenia were 24, 41, and 84, and 31%, respectively. The prevalence of frailty and cognitive impairment increased with aging, whereas the increase in sarcopenia prevalence plateaued after the age of 80 years. No significant differences were observed in the prevalence of frailty, cognitive impairment, and sarcopenia between the groups with and without diabetes mellitus, hypertension, or dyslipidemia with a few exceptions, presumably due to the high-risk subjects who had multiple cardiovascular comorbidities. A majority of the frail and sarcopenic patients revealed cognitive impairment, whereas the frequency of suspected dementia among these patients were both approximately 20%. Conclusions We found a high prevalence of frailty, cognitive impairment, and sarcopenia in patients with cardiometabolic disease in our frailty clinic. Comprehensive assessment of the high-risk patients could be useful to identify the risk factors for progression of frailty and cognitive decline.

Abstract Background Informal neighbor relationships (NRs) are considered a structural aspect of social relationships. Although NRs might affect physical activity (PA), no previous study has simultaneously examined compositional and contextual associations of NRs with PA. In this study, we examined whether individual- and community-level NRs were independently associated with PA. Methods We analyzed cross-sectional data from 8592 (4340 men and 4252 women) non-disabled residents aged 65–84 years from all 18 districts of Ota City, Tokyo. PA was assessed by using the International Physical Activity Questionnaire-Short Form. In addition, we calculated moderate-to-vigorous PA (MVPA), its components (vigorous PA [VPA], moderate PA [MPA], and walking time [WT]), and sitting time (ST). Individual-level NRs were categorized as “visiting each other,” “standing and chatting,” “exchange of greetings,” or “none.” Community-level NRs were defined as the proportions of residents with active NRs (i.e., those in the categories visiting each other and standing and chatting) in the 18 districts. Using multilevel regression analyses, we examined independent associations of individual- and community-level NRs with PA variables and adjusted for important confounders. Results Individual-level NRs were consistently positively associated with MVPA and its components (VPA, MPA [in men], and WT) in both sexes, and the dose–response relationships were significant (all P < 0.041 for trend). In men, community-level NRs (by 1% estimation) were positively associated with individual MVPA (2.1 metabolic equivalent-hours/week, 95% confidence interval: 0.7–3.4), VPA (8.6 min/week, 2.7–14.4), and WT (11.6 min/week, 2.2–20.9), regardless of the degree of individual-level NRs. Significant cross-level interactions of NRs with MVPA and VPA were observed among men, and the dose–response relationships were significant (both P

This study aimed to investigate the effects of occupational status and job stress factors on cardiovascular stress reactivity in Japanese workers. In this baseline assessment between 2001 and 2009 in Osaka, Japan, we examined 928 healthy Japanese employees (330 men, 598 women) from two occupational statuses: managers/professionals and general workers. A brief job stress questionnaire was used to evaluate job stress levels. Systolic and diastolic blood pressure (SBP, DBP), heart rate, heart rate variability (high-frequency [HF], low-frequency [LF], LF/HF], and peripheral blood flow were measured at rest and during two stressful tasks. Changes in stress reactivity were calculated as the difference between the measured variables during the tasks and the rest period. Men showed inverse associations between quantitative job overload and DBP, heart rate, and LF/HF, between physical demands and blood pressure (SBP, DBP), and between a poor physical environment and HF. Men also had positive associations between qualitative job overload and heart rate, and between physical demands and peripheral blood flow (all p

Background: Although apolipoprotein E polymorphism ε4 allele (ApoE4) and slow gait are well-known risk factors for cognitive impairment, examination of their combined effect on cognitive function is lacking. Our objective was to elucidate whether a combination of ApoE4 phenotyping and slow gait resulted in greater cognitive impairment.Methods: Overall, 1,085 community-dwelling older adults, either ApoE4 carriers (n = 167, 15.4%) or non-ApoE4 carriers, were included from the “Takashimadaira study.” Gait speed was assessed with an electronic walkway and slow gait was defined as

Augmented reality (AR) is an emerging technology in which information is superimposed onto the real world directly in front of observers. AR images may behave as distractors because they are inside the observer’s field of view and may cause observers to overlook important information in the real world. This kind of overlooking of events or objects is known as “change blindness.” In change blindness, a distractor may cause someone to overlook a change between an original image and a modified image. In the present study, we investigated whether change blindness occurs when AR is used and whether the AR presentation method influences change blindness. An AR image was presented binocularly or monocularly as a distractor in a typical flicker paradigm. In the binocular presentation, the AR image was presented to the both of the participants’ eyes, so, it was not different from the typical flicker paradigm. By contrast, in the monocular presentation, the AR image was presented to only one eye. Therefore, it was hypothesized that if participants could observe the real-world image through the eye to which the AR image was not presented, change blindness would be avoided because the moment of change itself could be observed. In addition, the luminance of the AR image was expected to influence the ease to observe the real world because the AR image is somewhat translucent. Hence, the AR distractor had three luminance conditions (high, medium, and low), and we compared how many alternations were needed to detect changes among the conditions. Result revealed that more alternations were needed in the binocular presentation and in the high luminance condition. However, in all luminance conditions in the monocular presentation, the number of alternations needed to detect the change was not significantly different from that when the AR distractor was not presented. This result indicates that the monocular presentation could attenuate change blindness, and this might be because the observers’ visual attention is attracted to the location where the change has occurred automatically.

OBJECTIVES:Recent studies reported that several gait parameters were associated with lower cognitive function or cognitive decline, however, known gait parameters were limited and no study has used large-scale data. We identified the characteristics for gait parameters of community-dwelling elderly Japanese with lower cognitive function. METHODS:1,240 community-dwelling adults (mean [SD] age, 77.2 [4.8] years; women, 59.4%) aged 70 or older participated in geriatric health assessments in 2016. We measured comprehensive gait parameters using resistive pressure platform. Cognition was assessed by Mini-Mental State Examination (MMSE). RESULTS:There are possible correlations between gait measures (gait speed, stride length, step length, step width, average foot pressure, double support duration, and single support duration) and CVs (CV of stride length, step length, average foot pressure, and single support duration) with MMSE score, respectively. After adjustment for important confounders, multiple regression models showed that gait speed (β = .080, p = 0.006), stride length (β = .123, p

[This corrects the article DOI: 10.1371/journal.pone.0206399.].

The psychological health effects of pet ownership have been widely studied, but only a few studies investigated its impact among socially isolated older adults. The present study aims to investigate the psychological health of older adults with or without the experience of pet (i.e., dog or cat) ownership who are socially isolated or not socially isolated. This study used cross-sectional data from 9856 community-dwelling older adults in a metropolitan area of Japan. Social and non-social isolation and type of pet ownership (i.e., dog or cat) were stratified to examine the psychological health. Logistic regression models indicated that, after adjusting for demographic and potential confounders, socially isolated older adults who never owned a dog were 1.22 times more likely to report lower psychological health in comparison to socially isolated current or past dog owners. No such difference was observed among cat owners. The results suggest that the experience of dog ownership may be effective to improve the psychological health among socially isolated older adult.

ObjectivesPrevious studies examined the physical characteristics of older dog owners. However, associations of health-related factors with dog/cat ownership have not been comprehensively evaluated. This cross-sectional study examined physical function, physical activity, social function, and psychological function of a population of community-dwelling older Japanese dog and cat owners after controlling for important confounders.MethodsThe analysis included data from 11,233 community-dwelling adults aged 65 years or older (51.5% women; 52.3% aged 75-84), in Ota City, Tokyo, Japan. Pet ownership experience and pet species owned were determined by self-reported questionnaire, and current, past, and never dog/cat ownership was analyzed.ResultsAnalysis of variables related to physical function and physical activity showed that motor fitness scale and walking activity were significantly associated with experience of dog ownership, after adjustment for important sociodemographic and health characteristics. Analysis of social function showed that interaction with neighbors, social isolation, and trust in neighbors were significantly associated with experience of dog ownership and cat ownership.ConclusionsAs compared with respondents with no history of pet ownership, motor fitness and walking activity are greater for dog owners and social function is higher for dog and cat owners. Caring for a dog or cat might be an effective health promotion strategy to increase physical activity and facilitate social participation among older adults.

BACKGROUND:The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. METHODS:Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. RESULTS:Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. CONCLUSION:Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.