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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.

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

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.

Promoting subjective well-being is a crucial challenge in aging societies. In 2022, we launched a community-based intervention trial (the Chofu-Digital-Choju Movement). This initiative centered on fostering in-person and online social connections to enhance the subjective well-being of older adults. This paper describes the study design and baseline survey. This quasi-experimental study involved community-dwelling older adults aged 65–84 years in Chofu City, Tokyo, Japan. A self-administered questionnaire was distributed to 3742 residents (1681 men and 2061 women), and a baseline survey was conducted in January 2022. We assessed subjective well-being (primary outcome); psychosocial, physical, and dietary factors; and the use of information and communication technology variables (secondary outcomes) among the participants. After the intervention involving online classes, community hubs, and community events, a 2-year follow-up survey will be conducted to evaluate the effects of the intervention, comparing the intervention group (participants) with the control group (non-participants). We received 2503 questionnaires (66.9% response rate); of these, the analysis included 2343 questionnaires (62.6% valid response rate; mean age, 74.4 (standard deviation, 5.4) years; 43.7% male). The mean subjective well-being score was 7.2 (standard deviation, 1.9). This study will contribute to the development of a prototype subjective well-being strategy for older adults.

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.

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

Developing environmental purification techniques for water resources is important for realising a sustainable society. Inorganic ion-exchanger is one of the research themes in technological development, particularly titania nanotubes (TNTs), which have been studied for the removal of cationic heavy metals and radionuclides. Although many studies have reported the adsorption properties of TNTs, the sorption behaviour and state of intercalated cations in the structure are still unclear. In this study, the sorption properties of Co2+, Ni2+, Zn2+, and Sr2+ on TNTs were investigated using the equilibrium isotherms, kinetics and detailed analysis of residues under simple batch conditions. The sorption isotherms of cations on TNTs were fitted with the Langmuir model, and the maximum sorption amount (Qmax) was in the order of Sr2+ (1.13 mmol/g) > Zn2+ (0.99 mmol/g) > Co2+ (0.85 mmol/g) > Ni2+ (0.78 mmol/g). The sorption kinetics data fitted well with pseudo second-order model. The X-ray analysis indicated that the Sr2+ sorption on TNTs resulted from the ion-exchange and formation of carbonate compounds. In contrast, the Co2+, Ni2+, and Zn2+ ions were estimated to be incorporated in an ionic state in the TNT interlayer by ion-exchange with Na+ and H+ via chelation with surface hydroxyl groups on TNTs. These results indicate that the crystallographic properties of TNTs, ionic size, and chemical property of the target cation, and reactivity with carbonic acid are important factors to consider in the design of water purification systems using TNTs.

Abstract Background Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke severity in patients with CE stroke divided by the type of AF. Methods Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between patients with PAF (n = 127) and PerAF (n = 231). Results Patients with PerAF were more likely to take oral anticoagulants (OACs) than those with PAF (37% vs. 13%, P 8) on admission (odds ratio [OR] to PAF = 1.80; 95% confidence interval [CI] 1.08–2.98; P = 0.02) and of an mRS score ≥ 3 at discharge (OR = 2.07; 95% CI 1.24–3.46; P = 0.006). Patients with PerAF had three times more internal carotid artery occlusion evaluated by magnetic resonance angiography, which indicated a more severe cerebral embolism compared with patients with PAF. Conclusions We found underuse of OAC in high risk AF patients with CE stroke. PerAF is significantly associated with severe stroke on admission and an unfavorable functional outcome at discharge in Japanese patients with CE stroke.

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

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.

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: 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

Pd nanoparticles were directly immobilized on acrylonitrile–butadiene–styrene copolymer (ABS), acrylonitrile–styrene copolymer (AS), polystyrene (PS), polyphenylene sulfide (PPS), poly(vinyl chloride) (PVC), polypropylene (PP), and polyethylene (PE) polymer substrates via chemical reactions induced by ionizing irradiation. X-ray photoelectron spectroscopy analysis revealed that the chemical state of the immobilized Pd nanoparticles depended on the polymer substrate type. Electroless plating was performed using the immobilized Pd nanoparticles as the catalyst, and Cu-plating films were deposited on all polymer substrates. The results of the tape-peeling test suggested that the chemical state of the immobilized Pd nanoparticles on the polymer substrates affected the plating adhesion strength. Notably, ABS with immobilized Pd particles exhibited a high adhesion strength beyond the practical level, even without prior chemical etching. It was presumed that the high adhesion strength was owing to the anchoring effect of the holes generated on the ABS surface by ionizing irradiation.

A new method has been developed to impart the antimicrobial activity of silver nanoparticles to resin substrates. A resin substrate immersed in an aqueous solution of silver nitrate was irradiated with gamma ray or high energy electron beams. Silver nanoparticles were successfully immobilized on the resin surface directly by chemical reactions induced by ionizing radiation. It was experimentally confirmed that various resin materials, such as acrylonitrile-butadiene-styrene, polyethylene, polypropylene, polyvinyl chloride, and polycarbonate, were applicable for this process. The effects of gamma ray or electron beam irradiation on resin substrates were almost negligible since the irradiation dose was equal or less than that used for sterilization. Despite the small amount of Ag loadings, the obtained samples showed high antibacterial and antiviral activities.

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.

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).

Pd nanoparticles were immobilized on an acrylonitrile–butadiene–styrene copolymer (ABS) substrate using ionizing radiation. The samples were prepared by irradiating plastic zipper packs containing ABS substrates and a Pd(NO3)2 aqueous solution with a high-energy electron beam (4.8 MeV). Pd nanoparticles immobilized on the ABS substrate surfaces were observed using scanning electron microscopy (SEM). The chemical state of Pd was found to be coordinated to a carbonyl group or a metallic state by X-ray photoelectron spectroscopy (XPS) measurements. The peel strength of the Cu film on the Pd/ABS samples was 0.7 N/mm or higher. This result shows that the prepared Pd/ABS samples have high adhesion strength, despite not undergoing treatments such as etching with chromic acid. This method is expected to immobilize metal nanoparticles, not only on plastic plates but also on various other materials.

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

Abstract Mesenchymal stem cell (MSC) therapies have been used in clinical trials in various fields. These cells are easily expanded, show low immunogenicity, can be acquired from medical waste, and have multiple functions, suggesting their potential applications in a variety of diseases, including liver disease and inflammatory bowel disease. MSCs help prepare the microenvironment, in response to inflammatory cytokines, by producing immunoregulatory factors that modulate the progression of inflammation by affecting dendritic cells, B cells, T cells, and macrophages. MSCs also produce a large amount of cytokines, chemokines, and growth factors, including exosomes that stimulate angiogenesis, prevent apoptosis, block oxidation reactions, promote remodeling of the extracellular matrix, and induce differentiation of tissue stem cells. According to ClinicalTrials.gov, more than 680 clinical trials using MSCs are registered for cell therapy of many fields including liver diseases (more than 40 trials) and inflammatory bowel diseases (more than 20 trials). In this report, we introduce background and clinical studies of MSCs in liver disease and inflammatory bowel diseases.

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.].

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

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.

Polydopamine (PDA)—a known adhesive coating material—was used herein to strongly immobilize a Pt-particle catalyst on an acrylonitrile−butadiene−styrene copolymer (ABS) substrate. Previous studies have shown that the poor adhesion between Pt particles and ABS surfaces is a considerable problem, leading to low catalytic durability for H2O2 decomposition during contact-lens cleaning. First, the ABS substrate was coated with PDA, and the PDA film was evaluated by X-ray photoelectron spectroscopy. Second, Pt particles were immobilized on the PDA-coated ABS substrate (ABS-PDA) using the electron-beam irradiation reduction method. The Pt particles immobilized on ABS-PDA (Pt/ABS-PDA) were observed using a scanning electron microscope. The Pt-loading weight was measured by inductively coupled plasma atomic emission spectroscopy. Third, the catalytic activity of the Pt/ABS-PDA was evaluated as the residual H2O2 concentration after immersing it in a 35,000-ppm H2O2 solution (the target value was less than 100 ppm). The catalytic durability was evaluated as the residual H2O2 concentration after repeated use. The PDA coating drastically improved both the catalytic activity and durability because of the high Pt-loading weight and strong adhesion among Pt particles, PDA, and the ABS substrate. Plasma treatment prior to PDA coating further improved the catalytic durability.

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: Brachial-ankle pulse wave velocity (baPWV) is inversely associated with cognitive function. However, it is not known whether baPWV predicts cognitive decline (CD) in later life. We examined whether or not baPWV is an independent risk marker of subsequent CD in a population of older Japanese. Methods: Among 982 adults aged 65 years or older who participated in a baseline survey, 526 cognitively intact adults (Mini-Mental State Examination [MMSE] score ≥24; mean [SD] age, 71.7 [5.6] years; women, 57.8%) were followed for a period of up to 5 years. Pulse wave velocity was determined using an automated waveform analyser. Cognition was assessed by the MMSE, and CD was defined as a decrease of two points or more on the MMSE. Results: During an average follow-up of 3.4 years, 85 participants (16.2%) developed CD. After controlling for important confounders, the odds ratios for CD in the highest and middle tertiles of baPWV, as compared with the lowest tertile, were 2.95 (95% confidence interval, 1.29–6.74) and 2.39 (95% confidence interval, 1.11–5.15), respectively. Conclusions: High baPWV was an independent predictor of CD in a general population of older adults and may be useful in the clinical evaluation of elders.

Cut-off values of habitual physical activity to determine mobility limitation (ML) would be useful for recommending modifications to life activities for community-dwelling older Japanese women. Accordingly, the aim of this study was to determine the levels of habitual physical activity (step counts: SC, moderate-vigorous physical activity: MVPA) capable of predicting ML in older women. This study included 630 community-dwelling older Japanese women (72.3 ± 5.9 years). ML was assessed in two consecutive self-reports, and defined as having some difficulty or being unable to walk one-quarter of a mile or climb 10 steps without resting. A uniaxial accelerometer continuously measured SC and MVPA for over 10 h/day for 7 days. Receiver operating characteristic analysis was conducted to determine the cut-off values of SC and MVPA that could predict ML. Results show that the prevalence of ML in this study was 28.3% (n = 178). The optimal cut-off values of SC and MVPA for predicting ML were 5,773 steps/day (sensitivity: 66.3%, specificity: 70.8%) and 107.4 min/week (sensitivity: 84.8%, specificity: 55.3%). It was concluded that the levels of SC and MVPA capable of predicting ML were 5,773 steps/day or 107.4 min/week for older Japanese women. Although these levels of habitual physical activity would be useful as an indicator in modifying the life activities in older Japanese women, the validity of the cut-off values for predicting ML will need to be confirmed in longitudinal studies.

In a previous study, Pt nanoparticles were supported on a substrate of acrylonitrile–butadiene–styrene copolymer (ABS) to give the ABS surface catalytic activity for H2O2 decomposition during contact lens cleaning. Although the Pt-particle/ABS catalysts exhibited considerably high specific catalytic activity for H2O2 decomposition, the catalytic activity decreased with increasing numbers of repeated usage, which meant the durability of the catalytic activity was low. Therefore, to improve the catalytic durability in this study, we proposed two types of pretreatments, as well as a combination of these treatments before supporting Pt nanoparticles on the ABS substrate. In the first method, the ABS substrate was etched, and in the second method, the surface charge of the ABS substrate was controlled. A combination of etching and surface charge control was also applied as a third method. The effects of these pretreatments on the surface morphology, surface chemical composition, deposition behavior of Pt particles, and Pt loading weight were investigated by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), cross-sectional SEM, and inductively coupled plasma atomic emission spectroscopy (ICP-AES), respectively. Both etching and controlling the surface charge effectively improved the catalytic durability for H2O2 decomposition. In addition, the combination treatment was the most effective.

To determine age- and sex-specific body composition reference values and investigate age differences in these parameters for community-dwelling older Japanese men and women, using direct segmental multi-frequency bioelectrical impedance analysis.We conducted a pooled analysis of data collected in four cohort studies between 2008 and 2012: Kusatsu Longitudinal Study, Hatoyama Cohort Study, Itabashi Cohort Study, and Kashiwa Cohort Study. The pooled analysis included cross-sectional data from 4478 nondisabled, community-dwelling adults aged 65-94 years (2145 men, 2333 women; mean age: 72.9 years in men and 72.6 years in women). Body weight, fat mass (FM), percentage FM, fat-free mass (FFM), and appendicular lean soft tissue mass were measured using the InBody 720 and 430 (Biospace Co. Ltd, Seoul, Korea). The values were then normalized by height in meters squared to determine body mass index (BMI), FM index (FMI), FFM index (FFMI), and skeletal muscle mass index (SMI).Simple means (standard deviation) of BMI, percentage FM, FMI, FFMI, and SMI were 23.4 (2.9) kg/m(2), 24.9 (6.3)%, 5.96 (2.09) kg/m(2), 17.4 (1.5) kg/m(2), and 7.29 (0.76) kg/m(2), respectively, in men and 22.7 (3.3) kg/m(2), 31.7 (7.1)%, 7.40 (2.61) kg/m(2), 15.3 (1.2) kg/m(2), and 5.86 (0.67) kg/m(2), respectively, in women. We then calculated quartiles and quintiles for these indices after stratifying for sex and 5-year age group. FFMI and SMI decreased significantly with age in both sexes (P < 0.001 for trends), but FFMI remained constant among the women with only a 1% decrease up to age 84 years. Percentage FM increased significantly, with age (P < 0.001 in men and P = 0.045 in women for trends), but FMI was unchanged in both sexes (P = 0.147 in men and P = 0.176 in women for trends).The present data should be useful in the clinical evaluation of body composition of older Japanese and for international comparisons. The small age-related decrease in FFMI may be a noteworthy characteristic of body composition change in older Japanese women.

A container used in contact lens cleaning requires a Pt plating weight of 1.5 mg for H2O2 decomposition although Pt is an expensive material. Techniques that decrease the amount of Pt are therefore needed. In this study, Pt nanoparticles instead of Pt plating film were supported on a substrate of acrylonitrile–butadiene–styrene copolymer (ABS). This was achieved by the reduction of Pt ions in an aqueous solution containing the ABS substrate using high-energy electron-beam irradiation. Pt nanoparticles supported on the ABS substrate (Pt-particle/ABS) had a size of 4–10 nm. The amount of Pt required for Pt-particle/ABS was 250 times less than that required for an ABS substrate covered with Pt plating film (Pt-film/ABS). The catalytic activity for H2O2 decomposition was estimated by measuring the residual H2O2 concentration after immersing the catalyst for 360 min. The Pt-particle/ABS catalyst had a considerably higher specific catalytic activity for H2O2 decomposition than the Pt-film/ABS catalyst. In addition, sterilization performance was estimated from the initial rate of H2O2 decomposition over 60 min. The Pt-particle/ABS catalyst demonstrated a better sterilization performance than the Pt-film/ABS catalyst. The difference between Pt-particle/ABS and Pt-film/ABS was shown to reflect the size of the O2 bubbles formed during H2O2 decomposition.

OBJECTIVES: To determine age- and sex-specific reference values for six physical performance measures, i.e. hand-grip strength, one-legged stance, and gait speed and step length at both usual and maximum paces, and to investigate age and sex differences in these measures among community-dwelling older Japanese adults. METHODS: We conducted a pooled analysis of data from six cohort studies collected between 2002 and 2011 as part of the Tokyo Metropolitan Institute of Gerontology-Longitudinal Interdisciplinary Study on Aging. The pooled analysis included cross-sectional data from 4683 nondisabled, community-dwelling adults aged 65 years or older (2168 men, 2515 women; mean age: 74.0 years in men and 73.9 years in women). RESULTS: Unweighted simple mean (standard deviation) hand-grip strength, one-legged stance, usual gait speed, usual gait step length, maximum gait speed, and maximum gait step length were 31.7 (6.7) kg, 39.3 (23.0) s, 1.29 (0.25) m/s, 67.7 (10.0) cm, 1.94 (0.38) m/s, and 82.3 (11.6) cm, respectively, in men and 20.4 (5.0) kg, 36.8 (23.4) s, 1.25 (0.27) m/s, 60.8 (10.0) cm, 1.73 (0.36) m/s, and 69.7 (10.8) cm, respectively, in women. All physical performance measures showed significant decreasing trends with advancing age in both sexes (all P

Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid). 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered 14C-hyaluronic acid was found in the blood. Approximately 90% of 14C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week) after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine.

This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects’ symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise.