Association of Cognitive Frailty with Physical Activity and Life-space in Patients on Hemodialysis: The REPnet- HD Study

Association of Cognitive Frailty with Physical Activity and Life-space in Patients on Hemodialysis: The REPnet- HD Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Cognitive Frailty with Physical Activity and Life-space in Patients on Hemodialysis: The REPnet- HD Study Takafumi Noji, Naoto Usui, Yoshifumi Abe, Sho Kojima, Daisuke Okamura, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6616447/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Nov, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Abstract Background Cognitive frailty in community-dwelling older adults is associated with decreased physical activity and limited life-space. However, the association between cognitive frailty, physical activity, and life-space in older patient undergoing hemodialysis (HD) is unknown. Here, we examined the association between cognitive frailty, physical activity and range of life-space mobility. Methods We enrolled 236 patients undergoing HD aged > 65 years (62% men, age 74 [70–79] years) in a multicenter prospective cohort study (REPnet-HD). Physical frailty was defined based on the revised Japanese version of the Cardiovascular Health Study criteria, and cognitive function was assessed using the Mini-Cog, with a score of < 3 points indicating cognitive impairment. Cognitive frailty was defined as the coexistence of physical frailty and cognitive impairment whereas robust was the absence of either. Life-space was assessed using the Life Space Assessment (LSA), and physical activity and sedentary behavior time were assessed using the International Physical Activity Questionnaire (IPAQ) short form. Low activity was defined based on the IPAQ results, sedentary was defined as median sedentary behavior time or longer, and low LSA was defined as an LSA < 40 points. Logistic regression analysis was performed using low activity, sedentary, and low LSA as dependent variables; the four groups based on physical frailty and cognitive impairment as independent variables (reference; robust), and age, sex, body mass index, comorbidities, albumin, and dialysis vintage as covariates. Results Physical and cognitive frailties were observed in 36.4% and 6.8% of the patients, respectively. Low activity was significantly associated with physical frailty (odds ratio [OR]; 3.67, 95% confidence interval [CI]; 1.85–7.26, p < 0.001) and cognitive frailty (OR;6.23, 95% CI; 1.28–30.45, p = 0.023). Sedentary was significantly associated with cognitive frailty (OR; 4.24, 95% CI; 1.20–14.86, p = 0.024). Low LSA was significantly associated with physical frailty (OR; 3.93, 95% CI; 1.94–7.93, p < 0.001) and cognitive frailty (OR; 7.82, 95% CI; 2.31–26.44 p < 0.001) with a higher OR for cognitive frailty. Conclusion Cognitive frailty may be associated with a higher risk of low activity due to a sedentary lifestyle and limited life space than physical frailty. cognitive frailty physical activity life-space sedentary behavior hemodialysis Figures Figure 1 Background In older adults, reduced physical activity and narrow life-space are associated with an increased risk of developing physical frailty and mortality [ 1 – 4 ]. The relationship between physical inactivity and mortality is consistent in patients undergoing hemodialysis (HD) [ 5 – 6 ]. Patients undergoing HD are prone to decreased physical activity due to dialysis-related hypotension [ 8 ] and fatigue [ 9 ], besides time constraints caused by dialysis treatment, with their physical activity reducing to 70% of healthy individuals of the same age. The Life Space Assessment (LSA) calculates scores based on “life-space,” “frequency,” “walking aids,” and “nursing care.” It has been reported that an increase in the extent of living is associated with an increase in physical activity in community-dwelling older adults [ 10 ]. In a report on community-dwelling older woman adults, it was reported that a narrow life-space is associated with the onset of dementia [ 11 ], and maintaining the life-space is also an important perspective in the onset of dementia. However, the actual status of the LSA in patients undergoing HD is unknown. Cognitive frailty is defined as the coexistence of physical frailty and cognitive impairment [ 12 ]. In community-dwelling older adults, cognitive frailty is reportedly associated with lower physical activity than physical frailty alone [ 13 ], major outcomes, such as the subsequent development of dementia [ 14 ], and an increased risk of mortality [ 15 ] Dementia in HD patients affects mortality and dialysis discontinuation [ 16 ] and has many detrimental effects on dialysis treatment management, such as self-extraction of needles during dialysis, making early intervention important to prevent progression to dementia. However, despite the higher prevalence of dementia in patients undergoing HD [ 17 ] and aging of the population recently [ 18 ], the association between cognitive frailty, physical activity, and range of life-space has not been reported in patients undergoing HD. We hypothesized that cognitive frailty would be more strongly associated with physical inactivity and reduced life-space than with physical frailty alone. This study aimed to clarify the association among cognitive frailty, physical activity, and life-space in older patients undergoing HD. Methods Study population This cross-sectional study included patients undergoing HD enrolled in the REPnet-HD study between January 2021 and August 2023 at 12 centers in Japan. The REPnet-HD was a multicenter prospective longitudinal observational study designed to determine the association between exercise habits, physical activity, and primary outcomes in patients undergoing HD. The inclusion criteria were patients aged ≥ 20 years old outpatient undergoing HD who consented to participate in the study. The exclusion criteria age < 65 years and missing primary data, such as physical function, physical activity, and LSA. This study was approved by the Ethics Committee of Juntendo University [approval number: 2020-2-001]. This study was registered with the University Hospital Medical Information Network Center [UMIN000050089]. Written informed consent was obtained from all the participants. Physical function and activities of daily living Physical function was assessed using handgrip strength and the Short Physical Performance Battery (SPPB). Handgrip strength was measured bilaterally using a hand dynamometer (Grip-D, TKK-.5401, Takei Kiki Kogyo), and the maximum value was used. The SPPB comprised a subscale of the 4-m usual gait speed, five times sit-to-stand, and standing balance tests. The SPPB task was rated on a scale of 0–4 and the total score was calculated [ 19 ]. The total SPPB score ranges from 0–12, with lower scores indicating worse physical function. Higher scores indicated better physical function. Activities of daily living (ADL) was assessed using the Barthel index [ 20 ]. Physical frailty Physical frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria[ 21 ], which included five components; 1) weight loss; > 2 kg in six months, 2) weakness; handgrip strength; men < 28 kg, women < 18 kg, 3) exhaustion; feeling inexplicably tired in the last two weeks, 4) slowness; usual walking speed < 1.0 m/s, 5) low physical activity; defined as a “less than once a week” response to the questions “Do you engage in moderate levels of physical exercise or sports aimed at health?” and “Do you engage in low levels of physical exercise aimed at health”. Of the five items, > 3 was considered physically frail, and 0–2 items were considered as having no physical frailty. Evaluation of cognitive frailty Cognitive function was assessed using the Mini-Cog©, which combines recall test and a clock-drawing test. The test was based on the Mini-Cog website ( https://Mini-Cog.com ). Patients were scored on a five-point scale (0 = worst, 5 = best), with a score of < 3 indicating cognitive impairment [ 22 ]. Cognitive frailty was defined as the coexistence of physical frailty and cognitive impairment [ 23 ]. Physical activity The physical activity was assessed using a Japanese version of the International Physical Activity Questionnaire (IPAQ) short form [ 24 ]. The IPAQ assesses the usual weekly amount of physical activity. The amount of activity for each intensity was calculated as metabolic equivalents (METs) using the following equations; physical activity (METs-min/week) = METS x daily time (min) x weekly days, in which walking activity is calculated as 3.3 METS, moderate physical activity as 4.0 METS, and vigorous physical activity as 8.0 METS. Total activity was calculated by sum of walking activity, moderate physical activity, and vigorous physical activity. In this study, low activity was defined as low physical activity if calculated according to the IPAQ guidelines [ 25 ], and the results corresponded to a low physical activity level. Sedentary behavior time was assessed using the IPAQ as the average time spent sitting or lying down on weekdays. There is no standard for sedentary activity time in patients undergoing HD. Therefore, we defined the group with a value higher than the median as sedentary. Life-space Assessment The LSA [ 26 ] is a questionnaire that assesses an individual’s usual range of activities during the previous month. The LSA was scored from 0–120 points assessed by subscale of life-space levels (bedroom to outside town), frequency of movement (less than once weekly, 1–3 times weekly, 4–6 times weekly, or daily), and use of assistance from equipment, such as walking aids and wheel chair or individuals (“yes” or “no”) in the past four weeks. Life-space levels were measured by asking; “During the past four weeks, have you been to other rooms of your home besides the room where you sleep; to an area outside your home such as your porch, deck or patio, hallway of an apartment building, or garage; to places in your neighborhood, other than your own yard or apartment building; to places outside your neighborhood but within your town; and to places outside your town?” The higher the score, the wider the range of activities of daily living. Previously, we defined a score of < 40 points as the low LSA group [ 27 ]. Other variables Other background characteristics, including age, sex, body mass index (BMI), dialysis vintage, comorbidities, and family structure, were collected from their medical records. Laboratory data included hemoglobin and albumin levels before dialysis. Statistical analysis Continuous variables are presented as mean (standard deviation) or median (25th–75th percentile). Categorical data are presented as the number of individuals (%), and patients were classified into four groups according to the presence or absence of physical frailty and cognitive impairment; (1) robust, (2) cognitive impairment, (3) physical frailty, and (4) cognitive frailty. One-way analysis of variance (ANOVA), Kruskal–Wallis test, and Chi-square test were used to compare the four groups, and the Bonferroni method was used as a post-hoc test if significant differences were found. Low activity, sedentary, and low LSA were used as dependent variables, whereas physical frailty, cognitive frailty, and cognitive dysfunction were used as independent variables (reference; robust or physical frailty). Multivariate logistic regression analysis was performed using age, sex, BMI, ischemic heart disease, diabetes mellitus, albumin levels, and dialysis vintage as covariates, which have been shown to be associated with physical activity and life-space in previous studies [ 28 – 31 ]. All statistical analyses were performed using SPSS version 29.0. Statistical significance was set at p < 0.05. Results The flow-chart in this study is shown in Fig. 1 . This study analyzed 236 of the 488 patients registered in the REPnet-HD study. We excluded 252 patients owing to aged < 65 years (n = 144), Mini-Cog not implemented (n = 7), LSA not implemented (n = 89), and cases with missing data (n = 12). Of the participants, 53.8% were robust, 3.0% had cognitive impairment, 36.4% had physical frailty, and 6.8% had cognitive frailty. Comparison of the patient characteristics among the four groups are presented in Table 1 . In the overall patients, the median age was 74.0 years, and 61.5% of the patients were men. Significant differences were found in age, dialysis vintage, and albumin levels between the robust and physical frailty groups (p < 0.05). Table 1 Comparison of physical function, physical activity, and life space among the four group Over All n = 236 Robust n = 127 Cognitive impairment n = 7 Physical frailty n = 86 Cognitive frailty n = 16 P-value Age (years) 74 (70–79) 73 (70–77) 78 (75–79) 76 (71–81) a 78.5(76–84) < 0.001 Man, n (%) 145 (61.5) 79 (62.2) 4 (57.1) 51 (59.3) 11 (68.8) 0.89 BMI (kg/m2) 22.3 ± 3.8 22.5 ± 3.51 21.7 ± 2.90 21.9 ± 4.36 22.1 ± 3.44 0.66 Dialysis vintage (year) 8.3 (4.8–13.2) 7.4 (4.3–10.4) 9.1 (7.6–16.1) 9.0 (5.6–14.8) a 9.8 (5.5–12.3) 0.04 Living alone, n (%) 53 (22.5) 28 (22.0) 2 (28.6) 20 (23.3) 3 (18.8) 0.07 Comorbidities, n (%) Ischemic heart disease 93 (39.4) 43 (33.9) 6 (85.7) 36 (41.9) 8 (50.0) 0.03 Diabetes 110 (46.6) 57 (44.9) 3 (42.9) 42 (48.8) 8 (50.0) 0.93 Cerebrovascular disease 45 (19.1) 23 (18.1) 2 (28.6) 17 (19.8) 3 (18.8) 0.91 Peripheral artery disease 52 (22.0) 20 (15.7) 2 (28.6) 23 (26.7) 7 (43.8) 0.03 Exercise therapy, n (%) 86 (36.4) 49 (38.6) 2 (28.6) 30 (34.9) 4 (25.0) 0.75 Laboratory data Albumin(g/dL) 3.5 (3.4–3.5) 3.6 (3.3–3.8) 3.1 (3.1–3.5) 3.4 (3.2–3.7) a 3.4 (3.2–3.4) < 0.001 Hemoglobin (g/dl) 10.6 (9.9–11.5) 10.5 (9.8–11.3) 10.3 (10.2–12.0) 10.8 (10.1–11.6) 10.8 (10.0–12.0) 0.66 Mean ± SD, Median (25th-75th percentile), n (%) a: vs. Robust p < 0.05, b: vs. Cognitive impairment p < 0.05, c: vs. Physical frailty p < 0.05 BMI, body mass index Comparison of physical function, physical activity, and LSA between the groups are shown in Table 2 . Compared with the robust group, the SPPB and its sub-items were significantly lower for the physical and cognitive frailty groups (p < 0.05). Among the sub-scales, only gait scores were lower for cognitive frailty than for physical frailty (p < 0.05). Balance scores were lower in the cognitive frailty group than in the cognitive impairment group(p < 0.05). Table 2 Comparison of physical function, physical activity, and life space among the four groups Over All n = 236 Robust n = 127 Cognitive impairment n = 7 Physical frailty n = 86 Cognitive frailty n = 16 P-value Handgrip strength (kg) 21.6 ± 7.5 24.5 ± 7.4 20.5 ± 6.7 18.1 ± 6.1 a 17.5 ± 4.9 a < 0.001 SPPB (point) 10 (8–12) 12 (10–12) 10 (8–11) 8 (4–11) a 6 (5–7) a < 0.001 Balance 4 (2–4) 4 (3–4) 4 (2–4) 2 (2–4) a 2 (2–2) a b < 0.001 Walking speed 4 (3–4) 4 (4–4) 4 (4–4) 3(2–4) a 2 (1–3) a b c < 0.001 Five times sit-to-stand 4 (2–4) 4 (3–4) 2 (2–4) 3(1–4) a 1 (1–2) a < 0.001 Barthel Index (point) 100 (100–100) 100 (100–100) 100 (97.5–100) 100 (91.2–100) a 97.5(86.3–100) a < 0.001 IPAQ (METs min/week) VPA 0 (0–0) 0 (0–0) 0 (0–0) 0(0–0) a 0 (0–0) 0.02 MPA 0 (0–0) 0 (0 -140) 0(0–60) 0(0–0) a 0 (0–0) a < 0.001 Walk activity 198 (0-693) 396 (99–957) 148 (0-346) 115(0- 379) a 0 (0-309) a < 0.001 Total activity 297 (0-967) 660 (198–1341) 148 (60–526) 135(0-517) a 0 (0- 309) a < 0.001 Sedentary behavior time (min) 420 (240–660) 360 (210–600) 480 (348–660) 480(300–840) a 660 (465–915) a < 0.001 LSA (point) 62.8 (32-86.6) 74 (60–91) 60 (28–78) 45.5(30–68) a 23.5(10–55) a < 0.001 Low activity, n (%) 150 (63.6) 62 (48.8) 5 (71.4) 69 (80.2) 14 (87.5) < 0.001 Sedentary, n (%) 113 (47.9) 50 (39.4) 4 (57.4) 47 (54.7) 12 (75.0) < 0.001 Low LSA, n (%) 70 (29.7) 19 (15.0) 3 (42.9) 38 (44.2) 10 (62.5) < 0.001 Mean (SD), Median (25th-75th percentile), n (%) a: vs. Robust p < 0.05, b: vs. Cognitive impairment p < 0.05, c: vs. Physical frailty p < 0.05 SPPB, Short Physical Performance Battery; VPA, Vigorous-intensity physical activity; MPA, Moderate Physical Activity Sedentary: Median 420 or higher Low LSA: Less than 40 points Scores on each of the physical activity items and LSA were significantly lower in the physical and cognitive frailty groups than in the robust group(p < 0.05). Sedentary behavior was significantly increased in the physical and cognitive frailty groups than in the robust group(p < 0.05). Low activity, sedentary, low LSA were significant difference between four groups, and were higher prevalence in the cognitive frailty group than in the other groups Logistic regression analysis, with robust as a reference, is presented in Table 3 . Physical frailty (odds ratio [OR]; 3.67, 95% confidence interval [CI]; 1.85–7.26, p < 0.001) and cognitive frailty (OR; 6.23, 95% CI; 1.28–30.45, p = 0.023) were associated with low activity. Sedentary was associated with cognitive frailty (OR; 4.24, 95% CI; 1.20–14.86, p = 0.024). Low LSA was associated with physical frailty (OR; 3.93, 95% CI; 1.94–7.93, p < 0.001) and cognitive frailty (OR; 7.82, 95% CI; 2.31–26.44 p < 0.001). Table 3 Logistic analysis of physical activity and life space(Reference: Robust) Univariated model Multivariated model Dependent variable Independent variable Odds ratio (95%CI) p-value Odds ratio (95%CI) p-value Low activity Robust Reference - Reference Cognitive impairment 1.45 (0.27–7.63) 0.662 1.53 (0.26-8.85) 0.638 Physical frailty 3.46 (1.86–6.43) < 0.001 3.67 (1.85-7.26) < 0.001 Cognitive frailty 4.32 (0.95–19.50) 0.056 6.23 (1.28–30.45) 0.023 Sedentary Robust Reference - Reference - Cognitive impairment 1.50 (0.32–6.71) 0.62 1.53 (0.29-7.89) 0.609 Physical frailty 1.53 (0.90–2.61) 0.116 1.81 (0.98–3.32) 0.057 Cognitive frailty 3.53 (1.11–11.30) 0.033 4.24 (1.20-14.86) 0.024 Low LSA Robust Reference - Reference - Cognitive impairment 1.85 (0.40–8.50) 0.44 3.54 (0.67–18.56) 0.134 Physical frailty 2.78 (1.56–4.97) < 0.001 3.93 (1.94–7.93) < 0.001 Cognitive frailty 4.45 (1.56–13.10) < 0.001 7.82 (2.31–26.44) < 0.001 The multivariate model was adjusted for age, sex, body mass index, diabetes mellitus, ischemic heart disease, albumin levels, and dialysis vintage Sedentary: Median 420 min or higher; LSA low scale: < 40 points CI Logistic regression analysis, with physical frailty as a reference, determined that cognitive frailty was associated with low activity (OR; 6.35 95% CI; 21.3–30.9 p = 0.022), sedentary (OR; 4.31, 95% CI; 1.23–15.1 p = 0.022), and low LSA (OR; 7.74, 95% CI; 2.29–26.2 p = 0.001) (Supplementary Table S1). Discussion To best of our knowledge, this study is the first report on the association between cognitive frailty and amount of physical activity and life-space in older patients undergoing HD. Our results showed that the prevalence of cognitive frailty was higher in older patients undergoing HD. Patients undergoing HD with cognitive frailty were more likely to have sedentary behavior, limited life-space than those with physical frailty alone and in a higher risk of physical inactivity. Therefore, our results suggest that it is necessary to design measures based on assessments for cognitive function and physical function to manage narrow life-space and physical inactivity in patients undergoing HD. This study showed that cognitive frailty was observed in 6.8% of older patients undergoing HD. In a meta-analysis in community-dwelling older adults, a prevalence rate of cognitive frailty was reported 0.9–40% [ 32 ], with wide variations among reports. Prevalence of cognitive frailty in previous studies conducted among community-dwelling older adults in Japan ranged from 1.2–2.7% [ 33 – 34 ], and the prevalence of cognitive frailty in this study was higher. This may be due to the clinical characteristics of older patients undergoing HD; patients with chronic kidney disease (CKD) have declined physical function as renal function declines with advanced CKD [ 35 ], and physical functions, such as handgrip strength and walking speed, are 60–70% lower in patients undergoing HD than in healthy participants [ 36 ]. A meta-analysis of patients undergoing HD showed that the prevalence of physical frailty was extremely high (40%) [ 37 ]. Furthermore, patients undergoing HD was 2.57 times more likely to have cognitive impairment than those not undergoing HD [ 17 ]. Moreover, the average age of patients undergoing HD is increasing [ 18 ], and poor nutrition, chronic inflammation, metabolic acidosis, insulin resistance, uremia, increased protein catabolism, multiple coexisting diseases, and amino acid loss during dialysis contribute to the progression of sarcopenia and worsens the frailty cycle [ 38 – 40 ]. These characteristics may contribute to a higher prevalence of cognitive frailty in in older patients undergoing HD than in community-dwelling older adults. Presently, cognitive frailty in older patients on HD was slower walking speed than physical frailty group, and was associated with narrow life-space and, low physical activity, which was similar to a previous study on community-dwelling older adults [ 13 ]. Furthermore, only cognitive frailty was independently associated with increased sedentary behavior. These results suggest that cognitive aspects rather than physical frailty are strongly associated with increased sedentary time. Cognitive and physical frailties have been reported to independently affect physical inactivity [ 13 , 41 ], and the results of the present study in patients undergoing HD were similar. Cognitive frailty is reportedly associated with aging, number of comorbidities, depression, social participation, and sedentary lifestyle [ 42 ]. Cognitive frailty reflects a different aspect of physical frailty and may increase the risk of physical inactivity. Therefore, besides physical frailty, screening for cognitive impairment using the Mini-Cog and other methods should be conducted to determine the effects of physical and cognitive functional aspects and take measures against declined physical activity and limited life- space. Here, the Mini-Cog score was used to define cognitive impairment. The cognitive assessment battery used to determine cognitive frailty varied among previous studies, which may have affected the prevalence of cognitive frailty in the present study. The Mini-Mental State Examination [ 43 ] and MoCA [ 44 ] are sensitive for more accurate assessment of cognitive impairment. The Mini-Cog is a cognitive function assessment comprising a three-item recall test and clock drawing test, and has the advantage of being a simple screening method. The present results showed that although the Mini-Cog was used to define cognitive frailty, it was more strongly associated with low activity than physical frailty alone. Therefore, a simple cognitive function assessment such as the Mini-Cog should be assessed as regular screening of cognitive function, and if cognitive impairment is progressive, the risk of physical activity and physical function decline may increase. It has been reported that the deterioration or improvement in cognitive frailty is related to age, balance ability, walking speed, comorbid diseases, exercise habits, and depressive symptoms [ 45 ]. Exercise is effective in preventing or improving cognitive deterioration [ 46 ]. A systematic review of patients on HD showed that physical activity did not worsen cognitive function [ 47 ], suggesting that it can prevent cognitive impairment. Considering these findings and the study results, it may be necessary to evaluate physical activity besides to physical and cognitive function assessments and consider clues for intervention in each case. One limitation of this study is that the number of cases of cognitive frailty was only 16, although the prevalence was higher than that in community-dwelling older adults in Japan, which may have led to uncertainty in the statistical estimates. Further studies are needed to increase the number of such cases. Because this was cross-sectional study, a causal relationship could not be identified. Therefore, a longitudinal study is needed to determine the causal relationship between cognitive and the primary outcomes of this population, such as narrowing of the scope of life, reduction in physical activity, and mortality Conclusions Cognitive frailty was found in 6.8% of older patients undergoing HD and independently associated with sedentary lifestyle and narrow life-space and may be associated with a higher risk of reduced physical activity than physical frailty alone. Abbreviations IPAQ: International Physical Activity Questionnaire VPA: vigorous-intensity physical activity MVPA, moderate to Vigorous physical activity LSA: life space assessment HD: hemodialysis SPPB: Short Physical Performance Battery ADL: activities of daily living BMI: body mass index ALB: albumin CKD: chronic kidney disease Declarations Acknowledgements The authors would like to thank the participants in this study, as well as the staff of collaborating institute and clinic, and Odawara nephrology clinic. We would like to thank Editage (www.editage.jp) for English language editing. Author contributions Research ideas and study design were contributed by T. N., N. U., Y. A, S. K., and M. S.; data acquisition was contributed by T. N., N. U., S. K., D. O., Y. S., S. N., S. N., K. M., M. N., Y. Y., and T. K.; data analysis/ interpretation was contributed by T. N., N. U., Y. A, S. K., and M. S.; statistical analysis was contributed by T.N; and supervision or mentorship was contributed by N.U., Y.A, and M.S. Each author contributed important intellectual content during the study, Funding This study was supported by JSPS KAKENHI (Grant no. 22K11346). Availability of data and materials. The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The Ethics Committee of Juntendo University approved this study (Approval No. 20-017), which was followed by ethical reviews at all institutions. Written informed consent was obtained from all participants. Consent for publication None Competing interests The authors declare no competing interests. All the authors have read and approved the final version of the manuscript. Registration This multicenter prospective cohort study investigated the effects of exercise and physical activity on functional decline, cardiovascular disease and mortality in patients undergoing hemodialysis. The trial registration number is R000057060. registration: 2023/01/20. URL of trial registry record: Trial registration: UMIN, UMIN000050089. Registered 2023/01/20, https://center6. umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057060 References Portegijs E, Rantakokko M, Viljanen A, Sipilä S, et al. Is frailty associated with life-space mobility and perceived autonomy in participation outdoors? A longitudinal study. Age Ageing. 2016;45(4):550-3. Tolley APL, Ramsey KA, Rojer AGM, et al. 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Association between dialysis treatment and cognitive decline: A study from the Project in Sado for Total Health (PROST), Japan. Geriatr Gerontol Int. 2017 ; 17(10):1584-1587. Canaud B, Tong L, Tentori F, et al. Clinical practices and outcomes in elderly hemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol. 2011;6(7):1651-62. Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: Association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49:M85–94. Mahoney FI, Barthel DW, et al. Functional evaluation: the Barthel index. Md State Med J. 1965 ; 14:61–5 Satake S, Arai H, et al. The Rev Japanese version of the cardiovascular health study criteria (revised J-CHS criteria). Geriatr Gerontol Int. 2020;20:992–3. Borson S, Scanlan J, Brush M, et al. The Mini-Cog: a cognitive ‘vital signs’ measure for dementia screening in multi‐lingual elderly. Int J Geriatr Psychiatry. 2000; 15(11):1021–1027. Yamamoto S, Yamasaki S, Higuchi S, et al. Prevalence and prognostic impact of cognitive frailty in elderly patients with heart failure: sub-analysis of FRAGILE-HF. ESC Heart Fail. 2022;9(3):1574-1583. Craig CL, Marshall AL, Sjöström M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381–95.24. Department of Public Health, Tokyo Medical University. Guidelines for Data Processing and Analysis of International Standardized Physical Activity Questionnaires - Short and Long Versions. https://www.tmu-ph.ac/news/data/180327_1.pdf (Access date: July 11, 2024) Harada K, Shimada H, Sawyer P, et al. Life‒space of community‒dwelling older adults using preventive health care services in Japan and the validity of composite scoring methods for assessment. Nihon Koshu Eisei Zasshi 2010( 57):526‒37 Saito, M. et al. Relationship between the method of commuting to a hemodialysis facility and physical activity and mobility in outpatients for hemodialysis, Journal of Dialysis Society of Japan. 2014 47(7): 421-426.. Tamura Y, Takahashi H, Sakai D, et al. Decreased Physical and Daily Living Activities in Patients with Peripheral Arterial Disease on Hemodialysis. J Clin Med. 2022;12(1):135 Sun F, Norman IJ, While AE er al. Physical activity in older people: a systematic review. BMC Public Health. 2013;13:449. Johansen KL, Chertow GM, Ng AV, Mulligan K, et al. Physical activity levels in patients on hemodialysis and healthy sedentary controls. Kidney Int. 2000;57(6):2564-70. Wahid A, Manek N, Nichols M, et al. Quantifying the Association Between Physical Activity and Cardiovascular Disease and Diabetes: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2016;5(9):e002495. Canevelli M, Cesari M, et al. Cognitive Frailty: Far From Clinical and Research Adoption. J Am Med Dir Assoc. 2017;18(10):816-818. Shimada H, Makizako H, Lee S,et al. Impact of Cognitive Frailty on Daily Activities in Older Persons. J Nutr Health Aging. 2016;20(7):729-35. Shimada H, Makizako H, Doi T, et al. Combined prevalence of frailty and mild cognitive impairment in a population of elderly Japanese people. J Am Med Dir Assoc. 2013 Jul;14(7):518-24. Hiraki K, Yasuda T, Hotta C, Izawa KP, Morio Y, Watanabe S, Sakurada T, Shibagaki Y, Kimura K. Decreased physical function in pre-dialysis patients with chronic kidney disease. Clin Exp Nephrol. 2013;17(2):225-31. Matsunaga A. Exercise intervention in dialysis patients. recent advances in sarcopenia and frailty in CKD. 2020, springer, pp: 85-110. https://doi.org/10.1007/978-981. Zhang F, Wang H, Bai Y, et al. Prevalence of physical frailty and impact on survival in patients with chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol. 2023;24(1):258. Hendriks FK, Smeets JSJ, van der Sande FM, et al. Dietary Protein and Physical Activity Interventions to Support Muscle Maintenance in End-Stage Renal Disease Patients on Hemodialysis. Nutrients. 2019;11(12):2972 Vettoretti S, Caldiroli L, Armelloni S, et al. Sarcopenia is Associated with Malnutrition but Not with Systemic Inflammation in Older Persons with Advanced CKD. Nutrients. 2019;11(6):1378. Kim JK, Choi SR, Choi MJ, Kim SG, et al. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clin Nutr. 2014 Feb;33(1):64-8. Zhao W, Hu P, Sun W, Wu W, et al. Effect of physical activity on the risk of frailty: A systematic review and meta-analysis. PLoS One. 2022;17(12): e0278226. Xie B, Ma C, Chen Y, et al. Prevalence and risk factors of the co-occurrence of physical frailty and cognitive impairment in Chinese community-dwelling older adults. Health Soc Care Community. 2021 ;29(1):294-303 Folstein MF et al. ““Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician, J Psychiatr Res, 1975;12:189–198. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. Suprawesta L, Chen SJ, Liang HY, et al. Factors affecting cognitive frailty improvement and progression in Taiwanese older adults. BMC Geriatr. 2024;24(1):105 Park H, Park JH, Na HR, et al. Combined Intervention of Physical Activity, Aerobic Exercise, and Cognitive Exercise Intervention to Prevent Cognitive Decline for Patients with Mild Cognitive Impairment: A Randomized Controlled Clinical Study. J Clin Med. 2019;8(7):940. Bogataj Š, Mesarič KK, Pajek M,et al. Physical exercise and cognitive training interventions to improve cognition in hemodialysis patients: A systematic review. Front Public Health.2022;10: 1032076. Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx Cite Share Download PDF Status: Published Journal Publication published 01 Nov, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6616447","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471698827,"identity":"dc30da00-38d7-4ec6-a0ca-a8e4c572bf64","order_by":0,"name":"Takafumi Noji","email":"","orcid":"","institution":"Department of Cardiac Rehabilitation, Odawara Cardiovascular Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takafumi","middleName":"","lastName":"Noji","suffix":""},{"id":471698829,"identity":"42dbea75-6b0a-45ea-a53d-d369805cd4d6","order_by":1,"name":"Naoto Usui","email":"","orcid":"","institution":"Department of Rehabilitation, Kisen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Naoto","middleName":"","lastName":"Usui","suffix":""},{"id":471698831,"identity":"911d2754-2ec1-4d90-9d53-c93495aa6f0d","order_by":2,"name":"Yoshifumi Abe","email":"","orcid":"","institution":"epartment of Rehabilitation Sciences, Faculty of Health Sciences, University of Tokyo Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yoshifumi","middleName":"","lastName":"Abe","suffix":""},{"id":471698834,"identity":"bd3d98dd-6183-45c5-ae7f-8e2215120096","order_by":3,"name":"Sho Kojima","email":"","orcid":"","institution":"Department of Rehabilitation, Kisen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sho","middleName":"","lastName":"Kojima","suffix":""},{"id":471698836,"identity":"fbf65285-7132-4530-b3b0-03a307b491f5","order_by":4,"name":"Daisuke Okamura","email":"","orcid":"","institution":"Department of Rehabilitation, St. Lukeʼs International Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Okamura","suffix":""},{"id":471698838,"identity":"1b0f53da-45e7-4f37-9d03-62493bf8d8a6","order_by":5,"name":"Yoichi Sato","email":"","orcid":"","institution":"Department of Rehabilitation, Uonuma Kikan Hospital,","correspondingAuthor":false,"prefix":"","firstName":"Yoichi","middleName":"","lastName":"Sato","suffix":""},{"id":471698839,"identity":"121b6cbd-1379-448a-8ab6-bf65c9b5fd2a","order_by":6,"name":"Nobuhito Shinozaki","email":"","orcid":"","institution":"Department of Rehabilitation, Tokatsu-Clinic Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nobuhito","middleName":"","lastName":"Shinozaki","suffix":""},{"id":471698842,"identity":"f92ecfa1-addf-4902-9607-fe6bf72b7006","order_by":7,"name":"Nobuyuki Shirai","email":"","orcid":"","institution":"Department of Rehabilitation, Niigata Rinko Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nobuyuki","middleName":"","lastName":"Shirai","suffix":""},{"id":471698843,"identity":"57ff4486-59dd-4484-a94f-8bf77ed9a525","order_by":8,"name":"Kenta Mikami","email":"","orcid":"","institution":"Department of Cardiac Rehabilitation, Iwatsuki-Minami Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kenta","middleName":"","lastName":"Mikami","suffix":""},{"id":471698844,"identity":"6f57878a-8c3a-401a-821d-069b4f93a763","order_by":9,"name":"Mizuki Nagashima","email":"","orcid":"","institution":"Department of Cardiac Rehabilitation, Iwatsuki-Minami Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mizuki","middleName":"","lastName":"Nagashima","suffix":""},{"id":471698845,"identity":"c497eda6-e992-475e-a75e-c64c2eb9970e","order_by":10,"name":"Yoji Yamada","email":"","orcid":"","institution":"Department of Physical Therapy, Faculty of Medical Sciences, Teikyo University of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yoji","middleName":"","lastName":"Yamada","suffix":""},{"id":471698846,"identity":"a763b923-2661-4786-8b3c-44fb5aef323b","order_by":11,"name":"Toshimasa Kasai","email":"","orcid":"","institution":"Department of Rehabilitation, Isawa Kyouritu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Toshimasa","middleName":"","lastName":"Kasai","suffix":""},{"id":471698847,"identity":"a4c428ac-b718-43ab-9cc0-be1435c524ae","order_by":12,"name":"Masakazu Saitoh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYLCCBBDBznzAAInLwIxfC1ARDzNbAlCLAZFaGMBaeEDKEVpwAt0G9ocfHv6wYbBn5vlQzLvjj5w5e/IBhh81DOzmOLSYHeAxlkhISAPawrvBmPeMgbFlz7MExp5jDMyWDTi1MAC1HIZqaTNI3HAjx4CBt4GB2eAALi3sj39AtPA8AGmpB2lh/ItXC4MZ1BYeBpCWBAOgFma8thzmMbNISEvj4TnMZmA4t83YcMOZZwmHZY5J4PbL8fbHN3/Y2Mixtzc/M3jbJidvcDz54MM3NTbJuEIMFmM8QMxmABMEOkki2QC7BlTdD5B5dsRoGQWjYBSMghEBABVcT5xiuvUMAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Physical Therapy, Faculty of Health Science, Juntendo University","correspondingAuthor":true,"prefix":"","firstName":"Masakazu","middleName":"","lastName":"Saitoh","suffix":""}],"badges":[],"createdAt":"2025-05-08 04:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6616447/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6616447/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11255-025-04882-8","type":"published","date":"2025-11-01T15:58:41+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84869080,"identity":"44341148-4847-4d62-9ef4-273dbbf21a9b","added_by":"auto","created_at":"2025-06-18 08:47:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63608,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of this study\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6616447/v1/112793516ff8cc54129b350c.png"},{"id":95041360,"identity":"84a21ddd-18f1-441f-b394-404056f9408e","added_by":"auto","created_at":"2025-11-03 16:11:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1009848,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6616447/v1/90f467f7-4eb6-4b65-aaa1-9748b21ed07c.pdf"},{"id":84869079,"identity":"0edf127b-7139-44e5-9b40-695a8ba97399","added_by":"auto","created_at":"2025-06-18 08:47:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16839,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6616447/v1/f16e6015cb5bad0ce82a50f2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of Cognitive Frailty with Physical Activity and Life-space in Patients on Hemodialysis: The REPnet- HD Study","fulltext":[{"header":"Background","content":"\u003cp\u003eIn older adults, reduced physical activity and narrow life-space are associated with an increased risk of developing physical frailty and mortality [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The relationship between physical inactivity and mortality is consistent in patients undergoing hemodialysis (HD) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Patients undergoing HD are prone to decreased physical activity due to dialysis-related hypotension [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and fatigue [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], besides time constraints caused by dialysis treatment, with their physical activity reducing to 70% of healthy individuals of the same age.\u003c/p\u003e \u003cp\u003eThe Life Space Assessment (LSA) calculates scores based on \u0026ldquo;life-space,\u0026rdquo; \u0026ldquo;frequency,\u0026rdquo; \u0026ldquo;walking aids,\u0026rdquo; and \u0026ldquo;nursing care.\u0026rdquo; It has been reported that an increase in the extent of living is associated with an increase in physical activity in community-dwelling older adults [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In a report on community-dwelling older woman adults, it was reported that a narrow life-space is associated with the onset of dementia [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and maintaining the life-space is also an important perspective in the onset of dementia. However, the actual status of the LSA in patients undergoing HD is unknown.\u003c/p\u003e \u003cp\u003eCognitive frailty is defined as the coexistence of physical frailty and cognitive impairment [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In community-dwelling older adults, cognitive frailty is reportedly associated with lower physical activity than physical frailty alone [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], major outcomes, such as the subsequent development of dementia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and an increased risk of mortality [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Dementia in HD patients affects mortality and dialysis discontinuation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and has many detrimental effects on dialysis treatment management, such as self-extraction of needles during dialysis, making early intervention important to prevent progression to dementia. However, despite the higher prevalence of dementia in patients undergoing HD [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and aging of the population recently [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], the association between cognitive frailty, physical activity, and range of life-space has not been reported in patients undergoing HD.\u003c/p\u003e \u003cp\u003eWe hypothesized that cognitive frailty would be more strongly associated with physical inactivity and reduced life-space than with physical frailty alone. This study aimed to clarify the association among cognitive frailty, physical activity, and life-space in older patients undergoing HD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThis cross-sectional study included patients undergoing HD enrolled in the REPnet-HD study between January 2021 and August 2023 at 12 centers in Japan. The REPnet-HD was a multicenter prospective longitudinal observational study designed to determine the association between exercise habits, physical activity, and primary outcomes in patients undergoing HD. The inclusion criteria were patients aged\u0026thinsp;\u0026ge;\u0026thinsp;20 years old outpatient undergoing HD who consented to participate in the study. The exclusion criteria age\u0026thinsp;\u0026lt;\u0026thinsp;65 years and missing primary data, such as physical function, physical activity, and LSA. This study was approved by the Ethics Committee of Juntendo University [approval number: 2020-2-001]. This study was registered with the University Hospital Medical Information Network Center [UMIN000050089]. Written informed consent was obtained from all the participants.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePhysical function and activities of daily living\u003c/h3\u003e\n\u003cp\u003ePhysical function was assessed using handgrip strength and the Short Physical Performance Battery (SPPB). Handgrip strength was measured bilaterally using a hand dynamometer (Grip-D, TKK-.5401, Takei Kiki Kogyo), and the maximum value was used. The SPPB comprised a subscale of the 4-m usual gait speed, five times sit-to-stand, and standing balance tests. The SPPB task was rated on a scale of 0\u0026ndash;4 and the total score was calculated [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The total SPPB score ranges from 0\u0026ndash;12, with lower scores indicating worse physical function. Higher scores indicated better physical function. Activities of daily living (ADL) was assessed using the Barthel index [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003ePhysical frailty\u003c/h3\u003e\n\u003cp\u003ePhysical frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which included five components; 1) weight loss; \u0026gt; 2 kg in six months, 2) weakness; handgrip strength; men\u0026thinsp;\u0026lt;\u0026thinsp;28 kg, women\u0026thinsp;\u0026lt;\u0026thinsp;18 kg, 3) exhaustion; feeling inexplicably tired in the last two weeks, 4) slowness; usual walking speed\u0026thinsp;\u0026lt;\u0026thinsp;1.0 m/s, 5) low physical activity; defined as a \u0026ldquo;less than once a week\u0026rdquo; response to the questions \u0026ldquo;Do you engage in moderate levels of physical exercise or sports aimed at health?\u0026rdquo; and \u0026ldquo;Do you engage in low levels of physical exercise aimed at health\u0026rdquo;. Of the five items, \u0026gt;\u0026thinsp;3 was considered physically frail, and 0\u0026ndash;2 items were considered as having no physical frailty.\u003c/p\u003e\n\u003ch3\u003eEvaluation of cognitive frailty\u003c/h3\u003e\n\u003cp\u003eCognitive function was assessed using the Mini-Cog\u0026copy;, which combines recall test and a clock-drawing test. The test was based on the Mini-Cog website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://Mini-Cog.com\u003c/span\u003e\u003cspan address=\"https://Mini-Cog.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Patients were scored on a five-point scale (0\u0026thinsp;=\u0026thinsp;worst, 5\u0026thinsp;=\u0026thinsp;best), with a score of \u0026lt;\u0026thinsp;3 indicating cognitive impairment [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Cognitive frailty was defined as the coexistence of physical frailty and cognitive impairment [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003ePhysical activity\u003c/h3\u003e\n\u003cp\u003eThe physical activity was assessed using a Japanese version of the International Physical Activity Questionnaire (IPAQ) short form [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The IPAQ assesses the usual weekly amount of physical activity. The amount of activity for each intensity was calculated as metabolic equivalents (METs) using the following equations; physical activity (METs-min/week)\u0026thinsp;=\u0026thinsp;METS x daily time (min) x weekly days, in which walking activity is calculated as 3.3 METS, moderate physical activity as 4.0 METS, and vigorous physical activity as 8.0 METS. Total activity was calculated by sum of walking activity, moderate physical activity, and vigorous physical activity. In this study, low activity was defined as low physical activity if calculated according to the IPAQ guidelines [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and the results corresponded to a low physical activity level.\u003c/p\u003e \u003cp\u003eSedentary behavior time was assessed using the IPAQ as the average time spent sitting or lying down on weekdays. There is no standard for sedentary activity time in patients undergoing HD. Therefore, we defined the group with a value higher than the median as sedentary.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLife-space Assessment\u003c/h2\u003e \u003cp\u003eThe LSA [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] is a questionnaire that assesses an individual\u0026rsquo;s usual range of activities during the previous month. The LSA was scored from 0\u0026ndash;120 points assessed by subscale of life-space levels (bedroom to outside town), frequency of movement (less than once weekly, 1\u0026ndash;3 times weekly, 4\u0026ndash;6 times weekly, or daily), and use of assistance from equipment, such as walking aids and wheel chair or individuals (\u0026ldquo;yes\u0026rdquo; or \u0026ldquo;no\u0026rdquo;) in the past four weeks. Life-space levels were measured by asking; \u0026ldquo;During the past four weeks, have you been to other rooms of your home besides the room where you sleep; to an area outside your home such as your porch, deck or patio, hallway of an apartment building, or garage; to places in your neighborhood, other than your own yard or apartment building; to places outside your neighborhood but within your town; and to places outside your town?\u0026rdquo; The higher the score, the wider the range of activities of daily living. Previously, we defined a score of \u0026lt;\u0026thinsp;40 points as the low LSA group [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOther variables\u003c/h3\u003e\n\u003cp\u003eOther background characteristics, including age, sex, body mass index (BMI), dialysis vintage, comorbidities, and family structure, were collected from their medical records. Laboratory data included hemoglobin and albumin levels before dialysis.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables are presented as mean (standard deviation) or median (25th\u0026ndash;75th percentile). Categorical data are presented as the number of individuals (%), and patients were classified into four groups according to the presence or absence of physical frailty and cognitive impairment; (1) robust, (2) cognitive impairment, (3) physical frailty, and (4) cognitive frailty.\u003c/p\u003e \u003cp\u003eOne-way analysis of variance (ANOVA), Kruskal\u0026ndash;Wallis test, and Chi-square test were used to compare the four groups, and the Bonferroni method was used as a post-hoc test if significant differences were found.\u003c/p\u003e \u003cp\u003eLow activity, sedentary, and low LSA were used as dependent variables, whereas physical frailty, cognitive frailty, and cognitive dysfunction were used as independent variables (reference; robust or physical frailty). Multivariate logistic regression analysis was performed using age, sex, BMI, ischemic heart disease, diabetes mellitus, albumin levels, and dialysis vintage as covariates, which have been shown to be associated with physical activity and life-space in previous studies [\u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. All statistical analyses were performed using SPSS version 29.0. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe flow-chart in this study is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This study analyzed 236 of the 488 patients registered in the REPnet-HD study. We excluded 252 patients owing to aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years (n\u0026thinsp;=\u0026thinsp;144), Mini-Cog not implemented (n\u0026thinsp;=\u0026thinsp;7), LSA not implemented (n\u0026thinsp;=\u0026thinsp;89), and cases with missing data (n\u0026thinsp;=\u0026thinsp;12). Of the participants, 53.8% were robust, 3.0% had cognitive impairment, 36.4% had physical frailty, and 6.8% had cognitive frailty.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComparison of the patient characteristics among the four groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In the overall patients, the median age was 74.0 years, and 61.5% of the patients were men. Significant differences were found in age, dialysis vintage, and albumin levels between the robust and physical frailty groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of physical function, physical activity, and life space among the four group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOver All\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;236\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRobust\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;127\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCognitive impairment\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePhysical frailty\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;86\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCognitive frailty\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (70\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (70\u0026ndash;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (75\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76 (71\u0026ndash;81) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e78.5(76\u0026ndash;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMan, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79 (62.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51 (59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis vintage (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.3 (4.8\u0026ndash;13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.4 (4.3\u0026ndash;10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.1 (7.6\u0026ndash;16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.0 (5.6\u0026ndash;14.8) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.8 (5.5\u0026ndash;12.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiving alone, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42 (48.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExercise therapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (38.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin(g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5 (3.4\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.6 (3.3\u0026ndash;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1 (3.1\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.4 (3.2\u0026ndash;3.7) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4 (3.2\u0026ndash;3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.6 (9.9\u0026ndash;11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5 (9.8\u0026ndash;11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.3 (10.2\u0026ndash;12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.8 (10.1\u0026ndash;11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.8 (10.0\u0026ndash;12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, Median (25th-75th percentile), n (%) a: vs. Robust p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, b: vs. Cognitive impairment p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, c: vs. Physical frailty p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003cp\u003eBMI, body mass index\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eComparison of physical function, physical activity, and LSA between the groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Compared with the robust group, the SPPB and its sub-items were significantly lower for the physical and cognitive frailty groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Among the sub-scales, only gait scores were lower for cognitive frailty than for physical frailty (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Balance scores were lower in the cognitive frailty group than in the cognitive impairment group(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of physical function, physical activity, and life space among the four groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOver All\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;236\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRobust\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;127\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCognitive impairment\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePhysical frailty\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;86\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCognitive frailty\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHandgrip strength (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSPPB (point)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (8\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (10\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (8\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (4\u0026ndash;11) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (5\u0026ndash;7) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBalance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2\u0026ndash;4) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (2\u0026ndash;2) \u003csup\u003ea b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalking speed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (4\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3(2\u0026ndash;4) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (1\u0026ndash;3) \u003csup\u003ea b c\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFive times sit-to-stand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3(1\u0026ndash;4) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (1\u0026ndash;2) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBarthel Index (point)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (97.5\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100 (91.2\u0026ndash;100) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e97.5(86.3\u0026ndash;100) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPAQ (METs min/week)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0\u0026ndash;0) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0 -140)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0\u0026ndash;0) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0\u0026ndash;0) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalk activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198 (0-693)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e396 (99\u0026ndash;957)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e148 (0-346)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e115(0- 379) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0-309) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e297 (0-967)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e660 (198\u0026ndash;1341)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e148 (60\u0026ndash;526)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e135(0-517) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0- 309) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSedentary behavior time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e420 (240\u0026ndash;660)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e360 (210\u0026ndash;600)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e480 (348\u0026ndash;660)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e480(300\u0026ndash;840) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e660 (465\u0026ndash;915) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSA (point)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.8 (32-86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (60\u0026ndash;91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (28\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.5(30\u0026ndash;68) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.5(10\u0026ndash;55) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow activity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (48.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69 (80.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSedentary, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e113 (47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47 (54.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow LSA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eMean (SD), Median (25th-75th percentile), n (%) a: vs. Robust p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, b: vs. Cognitive impairment p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, c: vs. Physical frailty p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003cp\u003eSPPB, Short Physical Performance Battery; VPA, Vigorous-intensity physical activity; MPA, Moderate Physical Activity\u003c/p\u003e \u003cp\u003eSedentary: Median 420 or higher Low LSA: Less than 40 points\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eScores on each of the physical activity items and LSA were significantly lower in the physical and cognitive frailty groups than in the robust group(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Sedentary behavior was significantly increased in the physical and cognitive frailty groups than in the robust group(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Low activity, sedentary, low LSA were significant difference between four groups, and were higher prevalence in the cognitive frailty group than in the other groups\u003c/p\u003e \u003cp\u003eLogistic regression analysis, with robust as a reference, is presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Physical frailty (odds ratio [OR]; 3.67, 95% confidence interval [CI]; 1.85\u0026ndash;7.26, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and cognitive frailty (OR; 6.23, 95% CI; 1.28\u0026ndash;30.45, p\u0026thinsp;=\u0026thinsp;0.023) were associated with low activity. Sedentary was associated with cognitive frailty (OR; 4.24, 95% CI; 1.20\u0026ndash;14.86, p\u0026thinsp;=\u0026thinsp;0.024). Low LSA was associated with physical frailty (OR; 3.93, 95% CI; 1.94\u0026ndash;7.93, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and cognitive frailty (OR; 7.82, 95% CI; 2.31\u0026ndash;26.44 p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic analysis of physical activity and life space(Reference: Robust)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eUnivariated model\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMultivariated model\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDependent variable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndependent variable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003cp\u003e(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003cp\u003e(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRobust\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.45 (0.27\u0026ndash;7.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.53 (0.26-8.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhysical frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.46 (1.86\u0026ndash;6.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.67 (1.85-7.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.32 (0.95\u0026ndash;19.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.23 (1.28\u0026ndash;30.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSedentary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRobust\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.50 (0.32\u0026ndash;6.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.53 (0.29-7.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhysical frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.53 (0.90\u0026ndash;2.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.81 (0.98\u0026ndash;3.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.53 (1.11\u0026ndash;11.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.24 (1.20-14.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow LSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRobust\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85 (0.40\u0026ndash;8.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.54 (0.67\u0026ndash;18.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhysical frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.78 (1.56\u0026ndash;4.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.93 (1.94\u0026ndash;7.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.45 (1.56\u0026ndash;13.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.82 (2.31\u0026ndash;26.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eThe multivariate model was adjusted for age, sex, body mass index, diabetes mellitus, ischemic heart disease, albumin levels, and dialysis vintage\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eSedentary: Median 420 min or higher; LSA low scale: \u0026lt; 40 points CI\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLogistic regression analysis, with physical frailty as a reference, determined that cognitive frailty was associated with low activity (OR; 6.35 95% CI; 21.3\u0026ndash;30.9 p\u0026thinsp;=\u0026thinsp;0.022), sedentary (OR; 4.31, 95% CI; 1.23\u0026ndash;15.1 p\u0026thinsp;=\u0026thinsp;0.022), and low LSA (OR; 7.74, 95% CI; 2.29\u0026ndash;26.2 p\u0026thinsp;=\u0026thinsp;0.001) (Supplementary Table S1).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo best of our knowledge, this study is the first report on the association between cognitive frailty and amount of physical activity and life-space in older patients undergoing HD. Our results showed that the prevalence of cognitive frailty was higher in older patients undergoing HD. Patients undergoing HD with cognitive frailty were more likely to have sedentary behavior, limited life-space than those with physical frailty alone and in a higher risk of physical inactivity. Therefore, our results suggest that it is necessary to design measures based on assessments for cognitive function and physical function to manage narrow life-space and physical inactivity in patients undergoing HD.\u003c/p\u003e \u003cp\u003eThis study showed that cognitive frailty was observed in 6.8% of older patients undergoing HD. In a meta-analysis in community-dwelling older adults, a prevalence rate of cognitive frailty was reported 0.9\u0026ndash;40% [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], with wide variations among reports. Prevalence of cognitive frailty in previous studies conducted among community-dwelling older adults in Japan ranged from 1.2\u0026ndash;2.7% [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], and the prevalence of cognitive frailty in this study was higher. This may be due to the clinical characteristics of older patients undergoing HD; patients with chronic kidney disease (CKD) have declined physical function as renal function declines with advanced CKD [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], and physical functions, such as handgrip strength and walking speed, are 60\u0026ndash;70% lower in patients undergoing HD than in healthy participants [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. A meta-analysis of patients undergoing HD showed that the prevalence of physical frailty was extremely high (40%) [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Furthermore, patients undergoing HD was 2.57 times more likely to have cognitive impairment than those not undergoing HD [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Moreover, the average age of patients undergoing HD is increasing [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and poor nutrition, chronic inflammation, metabolic acidosis, insulin resistance, uremia, increased protein catabolism, multiple coexisting diseases, and amino acid loss during dialysis contribute to the progression of sarcopenia and worsens the frailty cycle [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. These characteristics may contribute to a higher prevalence of cognitive frailty in in older patients undergoing HD than in community-dwelling older adults.\u003c/p\u003e \u003cp\u003ePresently, cognitive frailty in older patients on HD was slower walking speed than physical frailty group, and was associated with narrow life-space and, low physical activity, which was similar to a previous study on community-dwelling older adults [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Furthermore, only cognitive frailty was independently associated with increased sedentary behavior. These results suggest that cognitive aspects rather than physical frailty are strongly associated with increased sedentary time. Cognitive and physical frailties have been reported to independently affect physical inactivity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], and the results of the present study in patients undergoing HD were similar. Cognitive frailty is reportedly associated with aging, number of comorbidities, depression, social participation, and sedentary lifestyle [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Cognitive frailty reflects a different aspect of physical frailty and may increase the risk of physical inactivity. Therefore, besides physical frailty, screening for cognitive impairment using the Mini-Cog and other methods should be conducted to determine the effects of physical and cognitive functional aspects and take measures against declined physical activity and limited life- space.\u003c/p\u003e \u003cp\u003eHere, the Mini-Cog score was used to define cognitive impairment. The cognitive assessment battery used to determine cognitive frailty varied among previous studies, which may have affected the prevalence of cognitive frailty in the present study. The Mini-Mental State Examination [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] and MoCA [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] are sensitive for more accurate assessment of cognitive impairment. The Mini-Cog is a cognitive function assessment comprising a three-item recall test and clock drawing test, and has the advantage of being a simple screening method. The present results showed that although the Mini-Cog was used to define cognitive frailty, it was more strongly associated with low activity than physical frailty alone. Therefore, a simple cognitive function assessment such as the Mini-Cog should be assessed as regular screening of cognitive function, and if cognitive impairment is progressive, the risk of physical activity and physical function decline may increase.\u003c/p\u003e \u003cp\u003eIt has been reported that the deterioration or improvement in cognitive frailty is related to age, balance ability, walking speed, comorbid diseases, exercise habits, and depressive symptoms [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Exercise is effective in preventing or improving cognitive deterioration [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. A systematic review of patients on HD showed that physical activity did not worsen cognitive function [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e], suggesting that it can prevent cognitive impairment. Considering these findings and the study results, it may be necessary to evaluate physical activity besides to physical and cognitive function assessments and consider clues for intervention in each case.\u003c/p\u003e \u003cp\u003eOne limitation of this study is that the number of cases of cognitive frailty was only 16, although the prevalence was higher than that in community-dwelling older adults in Japan, which may have led to uncertainty in the statistical estimates. Further studies are needed to increase the number of such cases. Because this was cross-sectional study, a causal relationship could not be identified. Therefore, a longitudinal study is needed to determine the causal relationship between cognitive and the primary outcomes of this population, such as narrowing of the scope of life, reduction in physical activity, and mortality\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCognitive frailty was found in 6.8% of older patients undergoing HD and independently associated with sedentary lifestyle and narrow life-space and may be associated with a higher risk of reduced physical activity than physical frailty alone.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIPAQ: International Physical Activity Questionnaire\u003c/p\u003e\n\u003cp\u003eVPA: vigorous-intensity physical activity\u003c/p\u003e\n\u003cp\u003eMVPA, moderate to Vigorous physical activity\u003c/p\u003e\n\u003cp\u003eLSA: \u0026nbsp;life space assessment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHD: hemodialysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSPPB: Short Physical Performance Battery\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eADL: activities of daily living\u003c/p\u003e\n\u003cp\u003eBMI: \u0026nbsp;body mass index\u003c/p\u003e\n\u003cp\u003eALB: \u0026nbsp;albumin\u003c/p\u003e\n\u003cp\u003eCKD: chronic kidney disease\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors would like to thank the participants in this study, as well as the staff of collaborating institute and clinic, and Odawara nephrology clinic.\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.jp) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Research ideas and study design were contributed by T. N., N. U., Y. A, S. K., and M. S.; data acquisition was contributed by T. N., N. U., S. K., D. O., Y. S., S. N., S. N., K. M., M. N., Y. Y., and T. K.; data analysis/ interpretation was contributed by T. N., N. U., Y. A, S. K., and M. S.; statistical analysis was contributed by T.N; and supervision or mentorship was contributed by N.U., Y.A, and M.S. Each author contributed important intellectual content during the study,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study was supported by JSPS KAKENHI (Grant no. 22K11346).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of Juntendo University approved this study (Approval No. 20-017), which was followed by ethical reviews at all institutions. Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eAll the authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegistration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; This multicenter prospective cohort study investigated the effects of exercise and physical activity on functional decline, cardiovascular disease and mortality in patients undergoing hemodialysis. The trial registration number is R000057060. registration: 2023/01/20. URL of trial registry record: Trial registration: UMIN, UMIN000050089. Registered 2023/01/20, https://center6.\u003c/p\u003e\n\u003cp\u003eumin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057060\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePortegijs E, Rantakokko M, Viljanen A, Sipil\u0026auml; S, et al. Is frailty associated with life-space mobility and perceived autonomy in participation outdoors? A longitudinal study. Age Ageing. 2016;45(4):550-3.\u003c/li\u003e\n\u003cli\u003eTolley APL, Ramsey KA, Rojer AGM, et al. Objectively measured physical activity is associated with frailty in community-dwelling older adults: A systematic review. J Clin Epidemiol. 2021;137: 218-230.\u003c/li\u003e\n\u003cli\u003eWatanabe D, Yoshida T, Yamada Y et al. Dose-Response Relationship Between Life-Space Mobility and Mortality in Older Japanese Adults: A Prospective Cohort Study. J Am Med Dir Assoc. 2022;23(11): 1869.e7-1869.e18\u003c/li\u003e\n\u003cli\u003eLandi F, Cesari M, Onder G, et al. Physical activity and mortality in frail, community-living elderly patients. J Gerontol A Biol Sci Med Sci. 2004;59(8):833-7. \u003c/li\u003e\n\u003cli\u003eMatsuzawa R, Matsunaga A, Wang G, et al. Habitual physical activity measured by accelerometer and survival in maintenance hemodialysis patients. Clin J Am Soc Nephrol. 2012;7 :2010\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eMatsuzawa R, Roshanravan B, Shimoda T, et al. Physical activity dose for hemodialysis patients: where to begin? Results from a prospective cohort study. J Ren Nutr. 2018; 28:45\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eJohansen KL, Chertow GM, Ng AV, et al. Physical activity levels in patients on hemodialysis and healthy sedentary controls. Kidney Int. 2000;57(6):2564-70. \u003c/li\u003e\n\u003cli\u003eHattori K, Sakaguchi Y, Kajimoto S, et al. Intradialytic hypotension and objectively measured physical activity among patients on hemodialysis. J Nephrol. 2022;35(5):1409-1418.\u003c/li\u003e\n\u003cli\u003eMizuta S, Uchida K, Nakamura J et al. Association between fatigue and step counts on dialysis and non-dialysis days in hemodialysis outpatient. Journal of the Japanese Society for Renal Rehabilitation. 2024;3(1):61-68.\u003c/li\u003e\n\u003cli\u003eTsai LT, Portegijs E, Rantakokko M, Viljanen A, et al. The association between objectively measured physical activity and life-space mobility among older people. Scand J Med Sci Sports. 2015 ;25(4): e368-73. \u003c/li\u003e\n\u003cli\u003eSheets KM, Kats AM, Fink HA, et al. Life-space mobility and cognition in community-dwelling late-life women: A cross-sectional analysis. J Am Geriatr Soc. 2025 Jan;73(1):206-213. \u003c/li\u003e\n\u003cli\u003eKelaiditi E, Cesari M, Canevelli M, et al. IANA/IAGG. Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group. J Nutr Health Aging. 2013;17(9):726-34.\u003c/li\u003e\n\u003cli\u003eCorral-P\u0026eacute;rez J, Casals C, \u0026Aacute;vila-Cabeza-de-Vaca L, et al. Health factors associated with cognitive frailty in older adults living in the community. Front Aging Neurosci. 2023; 15: 1232460.\u003c/li\u003e\n\u003cli\u003eShimada H, Doi T, Lee S, et al. Cognitive frailty predicts incident dementia among community-dwelling older people. J Clin Med 2018; 7(9): 250.\u003c/li\u003e\n\u003cli\u003eQiu Y, Li G, Zheng L, et al. Relationship Between Cognitive Frailty and Mortality in Older Adults: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc. 2023;24(11):1637-1644.\u003c/li\u003e\n\u003cli\u003eKurella M, Mapes DL, Port FK, et al. Correlates and outcomes of dementia among dialysis patients: the Dialysis Outcomes and Practice Patterns Study. Nephrol Dial Transplant. 2006 Sep;21(9):2543-8\u003c/li\u003e\n\u003cli\u003eWatanabe Y, Kitamura K, Nakamura K, et al. Association between dialysis treatment and cognitive decline: A study from the Project in Sado for Total Health (PROST), Japan. Geriatr Gerontol Int. 2017 ; 17(10):1584-1587.\u003c/li\u003e\n\u003cli\u003eCanaud B, Tong L, Tentori F, et al. Clinical practices and outcomes in elderly hemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol. 2011;6(7):1651-62.\u003c/li\u003e\n\u003cli\u003eGuralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: Association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49:M85\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eMahoney FI, Barthel DW, et al. Functional evaluation: the Barthel index. Md State Med J. 1965 ; 14:61\u0026ndash;5\u003c/li\u003e\n\u003cli\u003eSatake S, Arai H, et al. The Rev Japanese version of the cardiovascular health study criteria (revised J-CHS criteria). Geriatr Gerontol Int. 2020;20:992\u0026ndash;3.\u003c/li\u003e\n\u003cli\u003eBorson S, Scanlan J, Brush M, et al. The Mini-Cog: a cognitive \u0026lsquo;vital signs\u0026rsquo; measure for dementia screening in multi‐lingual elderly. Int J Geriatr Psychiatry. 2000; 15(11):1021\u0026ndash;1027.\u003c/li\u003e\n\u003cli\u003eYamamoto S, Yamasaki S, Higuchi S, et al. Prevalence and prognostic impact of cognitive frailty in elderly patients with heart failure: sub-analysis of FRAGILE-HF. ESC Heart Fail. 2022;9(3):1574-1583.\u003c/li\u003e\n\u003cli\u003eCraig CL, Marshall AL, Sj\u0026ouml;str\u0026ouml;m M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381\u0026ndash;95.24. \u003c/li\u003e\n\u003cli\u003eDepartment of Public Health, Tokyo Medical University. Guidelines for Data Processing and Analysis of International Standardized Physical Activity Questionnaires - Short and Long Versions. https://www.tmu-ph.ac/news/data/180327_1.pdf (Access date: July 11, 2024)\u003c/li\u003e\n\u003cli\u003eHarada K, Shimada H, Sawyer P, et al. Life‒space of community‒dwelling older adults using preventive health care services in Japan and the validity of composite scoring methods for assessment. Nihon Koshu Eisei Zasshi 2010( 57):526‒37\u003c/li\u003e\n\u003cli\u003eSaito, M. et al. Relationship between the method of commuting to a hemodialysis facility and physical activity and mobility in outpatients for hemodialysis, Journal of Dialysis Society of Japan. 2014 47(7): 421-426..\u003c/li\u003e\n\u003cli\u003eTamura Y, Takahashi H, Sakai D, et al. Decreased Physical and Daily Living Activities in Patients with Peripheral Arterial Disease on Hemodialysis. J Clin Med. 2022;12(1):135\u003c/li\u003e\n\u003cli\u003eSun F, Norman IJ, While AE er al. 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Health Soc Care Community. 2021 ;29(1):294-303\u003c/li\u003e\n\u003cli\u003eFolstein MF et al. \u0026ldquo;\u0026ldquo;Mini-mental state\u0026rdquo;. A practical method for grading the cognitive state of patients for the clinician, J Psychiatr Res, 1975;12:189\u0026ndash;198.\u003c/li\u003e\n\u003cli\u003eNasreddine ZS, Phillips NA, B\u0026eacute;dirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9.\u003c/li\u003e\n\u003cli\u003eSuprawesta L, Chen SJ, Liang HY, et al. Factors affecting cognitive frailty improvement and progression in Taiwanese older adults. BMC Geriatr. 2024;24(1):105\u003c/li\u003e\n\u003cli\u003ePark H, Park JH, Na HR, et al. Combined Intervention of Physical Activity, Aerobic Exercise, and Cognitive Exercise Intervention to Prevent Cognitive Decline for Patients with Mild Cognitive Impairment: A Randomized Controlled Clinical Study. J Clin Med. 2019;8(7):940.\u003c/li\u003e\n\u003cli\u003eBogataj \u0026Scaron;, Mesarič KK, Pajek M,et al. Physical exercise and cognitive training interventions to improve cognition in hemodialysis patients: A systematic review. Front Public Health.2022;10: 1032076.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cognitive frailty, physical activity, life-space, sedentary behavior, hemodialysis","lastPublishedDoi":"10.21203/rs.3.rs-6616447/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6616447/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCognitive frailty in community-dwelling older adults is associated with decreased physical activity and limited life-space. However, the association between cognitive frailty, physical activity, and life-space in older patient undergoing hemodialysis (HD) is unknown. Here, we examined the association between cognitive frailty, physical activity and range of life-space mobility.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe enrolled 236 patients undergoing HD aged\u0026thinsp;\u0026gt;\u0026thinsp;65 years (62% men, age 74 [70\u0026ndash;79] years) in a multicenter prospective cohort study (REPnet-HD). Physical frailty was defined based on the revised Japanese version of the Cardiovascular Health Study criteria, and cognitive function was assessed using the Mini-Cog, with a score of \u0026lt;\u0026thinsp;3 points indicating cognitive impairment. Cognitive frailty was defined as the coexistence of physical frailty and cognitive impairment whereas robust was the absence of either. Life-space was assessed using the Life Space Assessment (LSA), and physical activity and sedentary behavior time were assessed using the International Physical Activity Questionnaire (IPAQ) short form. Low activity was defined based on the IPAQ results, sedentary was defined as median sedentary behavior time or longer, and low LSA was defined as an LSA\u0026thinsp;\u0026lt;\u0026thinsp;40 points. Logistic regression analysis was performed using low activity, sedentary, and low LSA as dependent variables; the four groups based on physical frailty and cognitive impairment as independent variables (reference; robust), and age, sex, body mass index, comorbidities, albumin, and dialysis vintage as covariates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePhysical and cognitive frailties were observed in 36.4% and 6.8% of the patients, respectively. Low activity was significantly associated with physical frailty (odds ratio [OR]; 3.67, 95% confidence interval [CI]; 1.85\u0026ndash;7.26, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and cognitive frailty (OR;6.23, 95% CI; 1.28\u0026ndash;30.45, p\u0026thinsp;=\u0026thinsp;0.023). Sedentary was significantly associated with cognitive frailty (OR; 4.24, 95% CI; 1.20\u0026ndash;14.86, p\u0026thinsp;=\u0026thinsp;0.024). Low LSA was significantly associated with physical frailty (OR; 3.93, 95% CI; 1.94\u0026ndash;7.93, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and cognitive frailty (OR; 7.82, 95% CI; 2.31\u0026ndash;26.44 p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with a higher OR for cognitive frailty.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCognitive frailty may be associated with a higher risk of low activity due to a sedentary lifestyle and limited life space than physical frailty.\u003c/p\u003e","manuscriptTitle":"Association of Cognitive Frailty with Physical Activity and Life-space in Patients on Hemodialysis: The REPnet- HD Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-18 08:46:55","doi":"10.21203/rs.3.rs-6616447/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"04d4129e-0289-45a6-a915-6685a1ea059a","owner":[],"postedDate":"June 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:09:52+00:00","versionOfRecord":{"articleIdentity":"rs-6616447","link":"https://doi.org/10.1007/s11255-025-04882-8","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2025-11-01 15:58:41","publishedOnDateReadable":"November 1st, 2025"},"versionCreatedAt":"2025-06-18 08:46:55","video":"","vorDoi":"10.1007/s11255-025-04882-8","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04882-8","workflowStages":[]},"version":"v1","identity":"rs-6616447","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6616447","identity":"rs-6616447","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}