The Connection Between Anemia and Limitations in Daily Activities Among Older Males: The Critical Role of Dynapenia

The Connection Between Anemia and Limitations in Daily Activities Among Older Males: The Critical Role of Dynapenia | 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 The Connection Between Anemia and Limitations in Daily Activities Among Older Males: The Critical Role of Dynapenia Abdulkadir Karismaz, Pinar Soysal, Rafet Eren, Istemi Serin, Ceyda Aslan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5053902/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Oct, 2024 Read the published version in Aging Clinical and Experimental Research → Version 1 posted 9 You are reading this latest preprint version Abstract Aim The aim of the present study was to examine the relationship between anemia and basic and instrumental activities of daily living in older male patients. Methods A total of 223 older males attending one geriatric outpatient clinic were included in this cross-sectional study. Anemia was defined as a hemoglobin level below 13 g/dL. Patients' demographic characteristics, comorbidities, and comprehensive geriatric assessment parameters were also recorded. Handgrip strength of < 27 kg for males was accepted as dynapenia. Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) questionnaires were used to evaluate functional capacity. Results The mean age (standard deviation) of the participants was 80.17 (7.69) years. The prevalence of patients with anemia was 43.9%. There was differences between anemic and non-anemic groups in terms of presence of diabetes mellitus (DM), congestive heart failure (CHF), chronic kidney disease (CKD), malnutrition, dynapenia, geriatric depression, BADL and IADL scores (all p < 0.05). In multivariate analysis, after adjusting for all confounding variables except for dynapenia, patients with anemia were associated with reduced BADL and IADL (all p < 0.05). After adjusting for all confounding variables including dynapenia, deterioration in total BADL and IADL scores did not remain significant in the anemic group compared to the non-anemic group (p > 0.05). Conclusion Close to one in two older outpatient men had anemia. Anemic men had a higher incidence of DM, CHF, CKD, malnutrition, geriatric depression and dynapenia. Anemia was associated with dependence in both BADL and IADL in older men. However, comorbidities, nutritional status, depressive mood and, specifically muscle strength, were important contributors to this association. older men anemia activities of daily living dynapenia 1. Introduction In the older population, anemia poses a substantial challenge, demonstrating a clear negative effect on the progression of coexisting conditions and longevity [ 1 – 3 ]. The overall prevalence of anemia stands at 17%, with variations across different settings: 12% in community-based studies, 47% in nursing homes, and 40% among hospital admissions [ 1 ]. The World Health Organization defines anemia as a condition where blood hemoglobin (Hb) levels fall below 12 g/dl for women and 13 g/dl for men. This condition is frequently observed in people aged 65 and older [ 4 ]. The occurrence of anemia tends to increase with advancing age and is slightly more prevalent in males compared to females [ 4 ]. Older individuals can develop anemia due to multiple factors. Among these, chronic disease is the most prevalent cause [ 5 – 7 ]. Several conditions more common in older adults, such as chronic infection, inflammatory disease, and malignancy, are linked to anemia caused by chronic disease. In the older population, iron deficiency is common and typically results from acute or chronic blood loss through the gastrointestinal system. In older individuals, additional significant contributors to anemia include deficiencies in folate and cobalamin (vitamin B12), which can result from insufficient intake or decreased absorption [ 5 , 8 ]. Furthermore, impaired kidney function is frequently observed in older patients [ 9 ]. Depending on the studied population, approximately 14–50% of anemia cases in the older have no clear identifiable cause [ 4 , 7 ]. Anemia serves as a significant indicator of unfavorable outcomes in later life, including increased risk of falls, disability, hospitalization, and death [ 10 – 11 ]. Research conducted over 4 and 11-year periods revealed that individuals with anemia face a mortality risk exceeding 50% compared to their non-anemic counterparts in older American populations [ 1 , 3 ]. The elevated mortality rate may be linked to inadequate oxygen delivery to body tissues, potentially leading to organ dysfunction and disruptions in essential bodily processes, thereby increasing the likelihood of death [ 12 – 13 ]. An increasing number of cross-sectional investigations indicate a connection between anemia and functional outcomes in older individuals, including dynapenia, which is characterized by the age-related reduction in muscle strength [ 14 – 16 ]. Research by Alexandre et al. revealed that anemia is linked to dynapenia in older Brazilian adults, while Cesari et al. discovered that anemic older Italian adults exhibit lower ankle extension strength compared to their non-anemic counterparts [ 14 , 17 ]. A comparable investigation conducted among older Korean adults revealed that those with anemia had a higher likelihood of experiencing dynapenia compared to their non-anemic counterparts. This relationship was found to be more significant in male participants than in females [ 18 – 19 ]. Anemia's impact on reducing oxygen delivery to tissues also impacts musculoskeletal structures, which may explain the diminished strength and muscle function observed in affected individuals [ 18 ]. These factors can collectively contribute to a reliance on assistance for daily living activities. However, there is currently no literature illuminating the relationship between anemia and functionality and related factors in older adults. Anemia can develop due to sex-based disparities. In males, for instance, anemia may be linked to insufficient sex hormone levels; nevertheless, a significant number of cases remain unexplained [ 20 – 21 ]. Anemia among men has not been given appropriate attention mainly owing to the lower number of the affected proportion when compared to women [ 22 ]. Indeed, the importance of anemia has been studied more in older women than in older men [ 23 ]. Considering the results mentioned, we hypothesized that there can be a significant relationship between anemia and the ability to perform basic and instrumental activities of daily living in older male patients. We also sought to obtain more accurate estimates by adjusting for potential key confounding factors, including decreased muscle strength [ 24 – 25 ]. Therefore, this study exclusively focused on older male participants due to the potential influence of hormonal, socioeconomic, and anthropometric variations between genders on the outcomes of anemia development and comprehensive geriatric assessment parameters. 2. Methods 2.1. Patients A total of 223 male patients who presented to one geriatric outpatient clinic in Turkey and underwent comprehensive geriatric assessment (CGA) were included in the study. One geriatrician and a gerontologist completed CGA in 45 minutes for each patient. All assessments were performed by the same geriatrician. The same team collected the study data. 2.2. Inclusion/exclusion criteria All male patients aged ≥ 65 years who presented to one geriatric outpatient clinic for any reason were included in the study. Female patients, patients with acute bleeding, including massive hematuria, hematochezia, melena, hematemesis, or intra-abdominal bleeding, patients with moderate and severe dementia, patients who were not able to undergo CGA due to their current clinical condition (e.g. delirium), patients who could not walk with an assistive device, those with localized muscle strength reduction due to stroke, those with severe visual and/or hearing impairment that prevented communication and understanding of commands during examination, those who refused to participate, those with a terminal disease (e.g. cancer), and those who were hospitalized for a life-threatening illness or major surgery in the last 6 months were not included in the study. As a result, 223 patients were available for study analysis. 2.3. Barthel Index for Activities of Daily Living (BADL) and Lawton Instrumental Activities of Daily Living (IADL) Scale The Barthel Index for Activities of Daily Living (BADL) measures the level of independence and functional status in basic daily activities like feeding, bathing, dressing, bowel/bladder control, using the toilet, transfers (from bed to chair), mobility (on flat surfaces), and stair climbing. A score of 100 indicates complete independence, whereas a score of 0 indicates complete dependency on another person [ 26 ]. Disability levels and other factors in community-dwelling older adults were first measured and evaluated by the researchers Lawton and Brody in 1969 using the Lawton Instrumental Activities of Daily Living Scale (IADL). The IADL, the most used assessment tool for this outcome in the older, measures eight abilities, including the use of a telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication, and ability to handle finances. Each activity is given a score ranging from 0 to between 2 and 4 in the Turkish version. Low scores indicate a high degree of dependency, and the scale runs from 0 to 23 [ 27 ]. 2.4. Comprehensive geriatric assessment Patients’ age, education level, and comorbidities including diabetes mellitus (DM), hypertension, coronary artery disease, chronic kidney disease (CKD), chronic obstructive pulmonary disease, cerebrovascular disease, congestive heart failure (CHF), peripheral artery disease, Parkinson’s Disease, and osteoarthritis were recorded. All participants underwent CGA including Standardized Mini-Mental State Examination (MMSE), Geriatric Depression Scale-15 for neurocognitive evaluation, Tinetti Performance-Oriented Assessment of Mobility (POMA) for mobility evaluation. Mini Nutritional Assessment (MNA) was performed in all patients to detect nutritional status. If the total MNA score was < 17, the patient was categorized as malnourished. Depression was diagnosed using the geriatric depression scale-15 (GDS-15). A score of ≥ 5 on the GDS-15 was considered as depression [ 28 ]. Calf circumference was assessed in sitting or supine position. For individuals in sitting position, measurements were taken on a chair in 90°-knee flexion with feet resting on the floor or on the footrest in a wheelchair. In the supine position, the knee joint was flexed at 90° with the feet and ankles relaxed. The flexible tape was wrapped perpendicular around the leg axis without pressing the tissue. Measurement was taken at maximum circumference [ 29 ]. Dynapenia Handgrip strength was assessed three times on each hand using the Jamar hand-held hydraulic dynamometer (Jamar hand dynamometer; Sammons Preston, Inc., Bolingbrook, IL, USA). Handle width was adjusted to hand size. Individuals were standing with their arms parallel to their trunk and were encouraged to squeeze the dynamometer as hard as possible. The maximal handgrip strength was recorded. A maximal handgrip strength of < 27 kg for males was accepted as dynapenia [ 30 ]. 2.5. Laboratory findings Laboratory tests were performed to evaluate inflammatory markers, the biochemical, metabolic, and nutritional status of the patients included complete blood count, kidney and liver functions, thyroid stimulating hormone, HbA1c and iron levels, iron-binding capacity (IBC), ferritin, vitamin B12, folic acid and vitamin D (25-hydroxy D3). Creatinine clearance from the kidney was estimated by the glomerular filtration rate (GFR) calculated using the chronic Renal Disease Epidemiology Collaborative (CKD-EPI) equation. Chronic Renal Failure (CRF) is defined as kidney damage or estimated GFR below 60 ml/min/1.73 m2. Anemia was defined as hemoglobin concentrations below 13 g/dL. 2.6. Statistical analyses Descriptive statistics of qualitative variables are presented as numbers and percentages, and the descriptive statistics of the quantitative variables are presented as mean, standard deviation, median, minimum, and maximum. The conformity of the quantitative variables to the normal distribution was evaluated with the Kolmogorov Smirnov test. The Mann Whitney U test was used to compare the mean of two independent groups. Pearson chi-square analysis was used for comparisons between the groups in terms of the ratios of the relevant qualitative variables. Logistic regression analysis was used to evaluate the relationships between the dependent variable and the independent variables. Enter method was used as variable selection method. The statistical significance level was taken as two-sided P ≤ 0.05, and the SPSS (version 26.0; IBM Corp, Armonk, NY, USA) package program was used for analyses. It was calculated that at least 198 older male patients needed to participate in the study with a 5% margin of error and a 95% confidence interval. 3. Results Of the 223 older male patients, 43.9% (n=98) had anemia. The mean age of the patients was 80.17±7.69 years. Patient characteristics, comorbidities, laboratory findings and geriatric syndromes/CGA parameters are summarized in Table 1. A significant difference was observed between the anemic and non-anemic groups in terms of the presence of DM, CKD and CHF (p 0.05) (Table 1). Numerous laboratory parameters differed between groups with and without anemia. While MCV, iron, IBC and GFR were lower in the group with anemia, red cell distribution width were higher. All CGA parameters were more negatively affected, except for MMSE, and geriatric syndromes were more common in patients with anemia compared to those without anemia (Table 1). Table 2 shows that after adjusting for age, in those with anemia compared to those without, adverse effects on malnutrition, dynapenia, BADL, IADL, and GDS scores were statistically significant ( p <0.05) (Model 2). In Model 3 multivariate analysis, adjustment was made according to age, DM, CHF, and CKD. BADL [OR: 0.95 (95% CI 0.93–0.98)], IADL [OR: 0.91 (95% CI: 0.87–0.97)], dynapenia [OR: 3.44 (95% CI: 1.78–6.66)], and malnutrition [OR: 4.07 (95% CI: 1.14–11.58)] scores were statistically significant (p < 0.05). In Model 4, in addition to the confounders in Model 3, GDS and malnutrition were added to the adjustment, and the significant association of anemia with deterioration in BADL and IADL scores remained (p < 0.05) (see Table 2). However, after adjustment Model 4+ Dynapenia, there was no significant relationship between anemia and ADL’s. Table 3 shows that after adjusting for age, DM, CHF and CKD, in those with anemia compared to those without, adverse effects on feeding [OR: 2.74 (95% CI: 1.18–6.36)], bathing [OR: 1.34 (95% CI: 1.01–1.76)], dressing [OR: 1.57 (95% CI: 1.02–2.42)], mobility [OR: 0.95 (95% CI: 0.91–0.98)], and stair climbing [OR: 1.49 (95% CI: 1.13–1.97)], scores were statistically significant ( p < 0.05) (Model 1). In Model 2, in addition to the confounders in Model 1, GDS and malnutrition were added to the adjustment, and significant associations were observed between anemia with mobility [OR: 1.84 (95% CI: 1.28–2.64)], and stair climbing [OR: 1.36 (95% CI: 1.02–1.81)] (p < 0.05). After adding dynapenia to the model, no significant relationship remained between anemia and each item of BADL’s. Table 4 shows that after adjusting for age, DM, CHF and CKD, in those with anemia compared to those with no anemia, adverse effects on shopping [OR: 1.23 (95% CI: 1.02–1.43)], food preparation [OR: 1.29 (95% CI: 1.08–1.53)], housekeeping [OR: 1.61 (95% CI: 1.08–2.41)] and mode of transportation [OR: 1.31 (95% CI: 1.10–1.55)] scores were statistically significant ( p < 0.05) (Model 1). In Model 2, in addition to the confounders in Model 1, GDS and malnutrition were added to the adjustment, and the significant association of anemia with shopping [OR: 1.18 (95% CI: 1.00–1.38)], food preparation [OR: 1.22 (95% CI: 1.02–1.46)] and mode of transportation [OR: 1.25 (95% CI: 1.05–1.49)] remained. After adding dynapenia, there was no significant relationship between anemia and each item of IADL’s. 4. Discussion This study investigated the relationship between anemia and basic and instrumental activities of daily living in older male patients. The frequency of DM, CHF, and CKD was higher in those with anemia than those without anemia. Among geriatric syndromes, depression, malnutrition and dynapenia were more common in anemic patients. Dependence on ADLs was higher in older men with anemia than in those without. However, this significant difference did not persist after adjustment for geriatric syndromes, especially dynapenia, that may affect this dependence. In older adults, anemia has multiple causes and is typically linked to socio-demographic characteristics, lifestyle choices, and chronic conditions including CKD, DM, and CVD, as well as deficiencies in nutrients such as iron, vitamin B12, and folate [30-32]. Nevertheless, in approximately 14% to 50% of elderly individuals, the underlying cause of anemia remains unidentified despite extensive examinations [6,32]. In the current study, we observed anemia (Hb level below 13 g/dl) in 98 (43.9%) of 223 patients. This prevalence value, independent of the etiology, is higher than the prevalence data obtained from other studies. Research findings on anemia prevalence in older men have shown varying results. In one study, Stauder et al. reported that 11% of elderly males were affected by anemia [33]. Conversely, a different investigation conducted by Awaluddin et al. discovered a higher prevalence rate of 30.7% among older men [34]. The observed differences could be attributed to several factors, including the older average age of our study population, as well as variations in racial and ethnic backgrounds, economic status, food preferences, and coexisting medical conditions. Conversely, research by Chan et al. revealed that anemia was present in 70.5% of elderly male residents in nursing homes [35]. This high prevalence can be attributed to several factors characteristic of this patient population, including reduced functional abilities, increased occurrence of frailty, and a higher incidence of additional health issues and geriatric conditions such as malnutrition. In present study, anemia in older men was found to be associated with DM, HT, CAD, and CKD. The relationship between these comorbid diseases and anemia and their possible mechanisms have previously been identified; thus, our results support these findings. A research study conducted by Michalak et al., involving 981 participants, revealed that 24.9% of patients were diagnosed with DM. Additionally, within the same investigation, 23.8% of a subgroup consisting of 105 elderly male subjects exhibited both anemia and DM [36]. In our study, the rate of patients with anemia and DM was calculated to be 44.9%. Multiple factors contribute to the development of anemia in DM. These include ongoing inflammation, lack of essential nutrients, reduced renin production, coexisting autoimmune conditions, concurrent use of certain HT medications (especially angiotensin II receptor blockers) and antihyperglycemic agents (particularly metformin), alterations in hormone levels, and impaired kidney function [37-38]. Additionally, men with type 2 DM frequently exhibit obesity, insulin resistance, and reduced testosterone levels, which could potentially elevate their risk of developing anemia [39]. In the presence of chronic kidney disease (CKD), erythropoietin production is impaired, leading to a primary hematologic manifestation characterized by severe hypoproliferative anemia [40]. Consequently, anemia may contribute to the advancement of chronic kidney disease, higher mortality rates, and a diminished quality of life. Since CKD is associated with geriatric syndromes that may negatively affect ADLs in the older adults, we adjusted for its effect in our study [41]. The same may also be true for anemia and CVD. The research conducted by Spazzafumo et al. revealed a link between anemia and increased cardiovascular risk [42]. Therefore, simultaneous treatment of anemia may be an important element of the management of these diseases. In the present study, we found that the dependence in both basic and instrumental life activities is more common in older men with anemia. This finding is consistent with previous studies. Research conducted by Maraldi et al. revealed that anemic males had a higher likelihood of experiencing impaired physical function and disability, with the risk increasing by a factor of 1.7 [43]. According to Maraldi et al., the inclusion of demographic and lifestyle factors in multivariate analysis only slightly reduced the strength of association. However, when nutritional factors and disease-related variables were considered, they observed a more substantial decrease in the strength of association. Consistent with previous research, this investigation revealed a strong correlation between anemia and dependency. However, when factors such as comorbidities, geriatric depression, and nutritional status were controlled for, the strength of this relationship decreased, though it remained statistically significant. However, we also evaluated the effect of dynapenia on this relationship, and showed that the connection between ADLs and anemia is largely due to dynapenia. Therefore, there is clear importance of anemia-related muscle weakness in an elderly male patient in maintaining independence in activities of daily living. Notably, when dynapenia and anemia occur together, they are strongly linked to an increased likelihood of death from any cause over a 10-year follow-up period. This association remains significant even after accounting for socioeconomic factors, lifestyle choices, and existing health conditions [44]. Anemia's impact on reducing oxygen delivery to tissues also impacts musculoskeletal structures, which may explain the diminished strength and muscle performance observed in anemic individuals [45]. These findings regarding anemia's effect on functional capacity clearly suggest a significant role of dynapenia [18]. One of the strengths of this study is the adequate sample size of patients with anemia. Another strength is that anemia screening and comprehensive geriatric evaluation were performed on the same day. A final strength is that only older men were included in the study; thus, sex-related effects could be excluded. Several limitations of this study should be considered when interpreting findings. Firstly, anemic men were not grouped among themselves according to the severity of anemia and were evaluated only at one visit. Second, erythropoietin levels were not routinely checked in all patients, which is important in deciding whether the anemia is transient or permanent. Another limitation of the study is that functional iron deficiency (transferrin saturation 100 ng/ml) was not examined in detail. Finally, the study utilized a cross-sectional design and thus direction of the observed association cannot be established it is possible that the relationship is bi-directional, for example, dependence in daily living may lead to malnutrition that subsequently leads to anemia. Future studies utilizing a longitudinal design are now required to elucidate on the direction of the association. In conclusion, approximately one in every two older men presenting to a Turkish outpatient clinic had anemia. Anemic men were older and had a higher incidence of DM, HT, CKD, malnutrition, geriatric depression and dynapenia. Anemia is associated with dependence in both basic and instrumental activities of daily living. However, dynapenia has an important contribution to this association. Therefore, older men should routinely be tested for anemia, anemia related reduced muscle strength should be investigated and treated in order to prevent dependency on daily life activities. Declarations Conflict of interest None. Ethical approval The study design and all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee of Bezmialem Vakif University—14/300) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Human and animal rights disclosure This article does not contain any studies with animals performed by any of the authors. Informed consent Informed consent was obtained from all individual participants included in the study. Competing interests The authors declare no competing interests. Author details 1 Department of Hematology, University of Health Sciences, Istanbul Training and Research Hospital, İstanbul, Turkiye. 2 Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkiye. 3 Department of Hematology, Biruni University Faculty of Medicine, Biruni University Hospital, Istanbul, Turkiye. 4 Department of Hematology, University of Health Sciences, Istanbul Basaksehir Cam and Sakura City Hospital, Istanbul, Turkiye. 5 Department of Hematology, Istinye University Faculty of Medicine, Liv Hospital, Istanbul, Turkiye. 6 Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran. 7 Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea. 8 Centre for Health Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK. Funding No funding was provided for this study. Author Contribution Design study: Abdulkadir KARISMAZ; practical performance: Abdulkadir KARISMAZ, Rafet EREN; data analysis: Pinar SOYSAL Istemi SERIN; preparation manuscript: Abdulkadir KARISMAZ, Dong Keon YON; critical review manuscript: Lee SMITH, Masoud RAHMATI. All authors contributed to the draft and revision of the manuscript and approved the version to be published. Acknowledgements The authors would like to acknowledge the participants. Availability of data and materials The datasets used and analyzed during the current study will be made available from the corresponding author on reasonable request. References Penninx BWJH, Pahor M, Woodman RC, Guralnik JM (2006) Anemia in old age is associated with increased mortality and hospitalization. J Gerontol Biol Sci Med Sci 61:474–479 Culleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR (2006) Impact of anemia on hospitalization and mortality in older adults. 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Aging Clin Exp Res 34(10):2483–2491 Perna S, Peroni G, Faliva MA et al (2017) Sarcopenia and sarcopenic obesity in comparison: prevalence, metabolic profile, and key differences. A cross-sectional study in Italian hospitalized elderly. Aging Clin Exp Res 29(6):1259 Luiz MM, Schneider IJC, Kuriki HU et al (2022 Sep-Oct) The combined effect of anemia and dynapenia on mortality risk in older adults: 10-Year evidence from the ELSA cohort study. Arch Gerontol Geriatr 102:104739 Dodd SL, Powers SK, Brooks E, Crawford MP (1993) Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle. J Appl Physiol 74(1):186–191 Hammer T, Braisch U, Rothenbacher D, Denkinger M, Dallmeier D (2024) Relationship between hemoglobin and grip strength in older adults: the ActiFE study. Aging Clin Exp Res 36(1):59 Tables Table 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files maletablo1.docx maletablo2.docx Cite Share Download PDF Status: Published Journal Publication published 26 Oct, 2024 Read the published version in Aging Clinical and Experimental Research → Version 1 posted Editorial decision: Revision requested 14 Sep, 2024 Reviews received at journal 14 Sep, 2024 Reviews received at journal 09 Sep, 2024 Reviewers agreed at journal 09 Sep, 2024 Reviewers agreed at journal 09 Sep, 2024 Reviewers invited by journal 09 Sep, 2024 Editor assigned by journal 09 Sep, 2024 Submission checks completed at journal 09 Sep, 2024 First submitted to journal 08 Sep, 2024 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. 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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-5053902","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":354106988,"identity":"116176f0-66ab-4735-988e-ad57f0b1e2d4","order_by":0,"name":"Abdulkadir Karismaz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYBACCR4gkQBisfeABXj4iNfCc4aB4QCQYiNKC4SVA9bCQFCLZM/hZx8e/NkmLz/z7cHHH3PsZNgYmB8+uoFHizRvm/GMxLbbho2z85INDm5LBjqMzdg4B48WOX4GY4bEhtuMzdI5ZhIHtzEDtfCwSePXwv6ZIeHPbfs2yTMgLfWEtUjz9hgzJLDdTuyR4AFpOUxYi2TPmWIGoF+SZ/DkGBuc3Xach42ZgF8kzqRvZvzx57bt/PYzhg8qt1Xb87M3P3yMTwsWwEya8lEwCkbBKBgFWAAAYoBEIRlSYdEAAAAASUVORK5CYII=","orcid":"","institution":"University of Health Sciences, Istanbul Training and Research Hospital","correspondingAuthor":true,"prefix":"","firstName":"Abdulkadir","middleName":"","lastName":"Karismaz","suffix":""},{"id":354106989,"identity":"8240698a-d351-4e13-8431-fb6395667a7b","order_by":1,"name":"Pinar Soysal","email":"","orcid":"","institution":"Bezmialem Vakif 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ceyda","middleName":"","lastName":"Aslan","suffix":""},{"id":354106994,"identity":"a268f790-c0a9-4836-92d5-6333d5919768","order_by":5,"name":"Masoud Rahmati","email":"","orcid":"","institution":"Lorestan University","correspondingAuthor":false,"prefix":"","firstName":"Masoud","middleName":"","lastName":"Rahmati","suffix":""},{"id":354106997,"identity":"7de85992-6cb5-485b-96f2-8f42e1e53315","order_by":6,"name":"Dong Keon Yon","email":"","orcid":"","institution":"Kyung Hee University Medical Center, Kyung Hee University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"Keon","lastName":"Yon","suffix":""},{"id":354106998,"identity":"9e67b56f-d914-4e93-af15-863b6de99d66","order_by":7,"name":"Lee Smith","email":"","orcid":"","institution":"Anglia Ruskin University","correspondingAuthor":false,"prefix":"","firstName":"Lee","middleName":"","lastName":"Smith","suffix":""}],"badges":[],"createdAt":"2024-09-08 18:44:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5053902/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5053902/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s40520-024-02859-8","type":"published","date":"2024-10-26T15:57:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67681726,"identity":"b08a42ca-a4eb-4086-9df4-ab5745eecd36","added_by":"auto","created_at":"2024-10-28 16:08:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":495557,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5053902/v1/5a1f7bb2-f2ad-445d-b38c-97fd0ae64f56.pdf"},{"id":66738449,"identity":"debc8c70-3fcf-490d-9b35-ac421ea2e5c1","added_by":"auto","created_at":"2024-10-16 05:24:27","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":17998,"visible":true,"origin":"","legend":"","description":"","filename":"maletablo1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5053902/v1/3bb22662dd5be1b383febb8f.docx"},{"id":66738562,"identity":"774dd3b5-fda1-420b-9a87-ad2d6d4034dd","added_by":"auto","created_at":"2024-10-16 05:24:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":20919,"visible":true,"origin":"","legend":"","description":"","filename":"maletablo2.docx","url":"https://assets-eu.researchsquare.com/files/rs-5053902/v1/149152d41dbf6afafde2d3a2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Connection Between Anemia and Limitations in Daily Activities Among Older Males: The Critical Role of Dynapenia","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eIn the older population, anemia poses a substantial challenge, demonstrating a clear negative effect on the progression of coexisting conditions and longevity [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The overall prevalence of anemia stands at 17%, with variations across different settings: 12% in community-based studies, 47% in nursing homes, and 40% among hospital admissions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The World Health Organization defines anemia as a condition where blood hemoglobin (Hb) levels fall below 12 g/dl for women and 13 g/dl for men. This condition is frequently observed in people aged 65 and older [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The occurrence of anemia tends to increase with advancing age and is slightly more prevalent in males compared to females [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Older individuals can develop anemia due to multiple factors. Among these, chronic disease is the most prevalent cause [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Several conditions more common in older adults, such as chronic infection, inflammatory disease, and malignancy, are linked to anemia caused by chronic disease. In the older population, iron deficiency is common and typically results from acute or chronic blood loss through the gastrointestinal system. In older individuals, additional significant contributors to anemia include deficiencies in folate and cobalamin (vitamin B12), which can result from insufficient intake or decreased absorption [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Furthermore, impaired kidney function is frequently observed in older patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Depending on the studied population, approximately 14\u0026ndash;50% of anemia cases in the older have no clear identifiable cause [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnemia serves as a significant indicator of unfavorable outcomes in later life, including increased risk of falls, disability, hospitalization, and death [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Research conducted over 4 and 11-year periods revealed that individuals with anemia face a mortality risk exceeding 50% compared to their non-anemic counterparts in older American populations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The elevated mortality rate may be linked to inadequate oxygen delivery to body tissues, potentially leading to organ dysfunction and disruptions in essential bodily processes, thereby increasing the likelihood of death [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. An increasing number of cross-sectional investigations indicate a connection between anemia and functional outcomes in older individuals, including dynapenia, which is characterized by the age-related reduction in muscle strength [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Research by Alexandre et al. revealed that anemia is linked to dynapenia in older Brazilian adults, while Cesari et al. discovered that anemic older Italian adults exhibit lower ankle extension strength compared to their non-anemic counterparts [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A comparable investigation conducted among older Korean adults revealed that those with anemia had a higher likelihood of experiencing dynapenia compared to their non-anemic counterparts. This relationship was found to be more significant in male participants than in females [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Anemia's impact on reducing oxygen delivery to tissues also impacts musculoskeletal structures, which may explain the diminished strength and muscle function observed in affected individuals [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These factors can collectively contribute to a reliance on assistance for daily living activities. However, there is currently no literature illuminating the relationship between anemia and functionality and related factors in older adults.\u003c/p\u003e \u003cp\u003eAnemia can develop due to sex-based disparities. In males, for instance, anemia may be linked to insufficient sex hormone levels; nevertheless, a significant number of cases remain unexplained [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Anemia among men has not been given appropriate attention mainly owing to the lower number of the affected proportion when compared to women [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Indeed, the importance of anemia has been studied more in older women than in older men [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Considering the results mentioned, we hypothesized that there can be a significant relationship between anemia and the ability to perform basic and instrumental activities of daily living in older male patients. We also sought to obtain more accurate estimates by adjusting for potential key confounding factors, including decreased muscle strength [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, this study exclusively focused on older male participants due to the potential influence of hormonal, socioeconomic, and anthropometric variations between genders on the outcomes of anemia development and comprehensive geriatric assessment parameters.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Patients\u003c/h2\u003e \u003cp\u003eA total of 223 male patients who presented to one geriatric outpatient clinic in Turkey and underwent comprehensive geriatric assessment (CGA) were included in the study. One geriatrician and a gerontologist completed CGA in 45 minutes for each patient. All assessments were performed by the same geriatrician. The same team collected the study data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Inclusion/exclusion criteria\u003c/h2\u003e \u003cp\u003eAll male patients aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years who presented to one geriatric outpatient clinic for any reason were included in the study. Female patients, patients with acute bleeding, including massive hematuria, hematochezia, melena, hematemesis, or intra-abdominal bleeding, patients with moderate and severe dementia, patients who were not able to undergo CGA due to their current clinical condition (e.g. delirium), patients who could not walk with an assistive device, those with localized muscle strength reduction due to stroke, those with severe visual and/or hearing impairment that prevented communication and understanding of commands during examination, those who refused to participate, those with a terminal disease (e.g. cancer), and those who were hospitalized for a life-threatening illness or major surgery in the last 6 months were not included in the study. As a result, 223 patients were available for study analysis.\u003c/p\u003e \u003cp\u003e \u003cb\u003e2.3. Barthel Index for Activities of Daily Living (BADL) and Lawton Instrumental Activities of Daily Living (IADL) Scale\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe Barthel Index for Activities of Daily Living (BADL) measures the level of independence and functional status in basic daily activities like feeding, bathing, dressing, bowel/bladder control, using the toilet, transfers (from bed to chair), mobility (on flat surfaces), and stair climbing. A score of 100 indicates complete independence, whereas a score of 0 indicates complete dependency on another person [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDisability levels and other factors in community-dwelling older adults were first measured and evaluated by the researchers Lawton and Brody in 1969 using the Lawton Instrumental Activities of Daily Living Scale (IADL). The IADL, the most used assessment tool for this outcome in the older, measures eight abilities, including the use of a telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication, and ability to handle finances. Each activity is given a score ranging from 0 to between 2 and 4 in the Turkish version. Low scores indicate a high degree of dependency, and the scale runs from 0 to 23 [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Comprehensive geriatric assessment\u003c/h2\u003e \u003cp\u003ePatients\u0026rsquo; age, education level, and comorbidities including diabetes mellitus (DM), hypertension, coronary artery disease, chronic kidney disease (CKD), chronic obstructive pulmonary disease, cerebrovascular disease, congestive heart failure (CHF), peripheral artery disease, Parkinson\u0026rsquo;s Disease, and osteoarthritis were recorded. All participants underwent CGA including Standardized Mini-Mental State Examination (MMSE), Geriatric Depression Scale-15 for neurocognitive evaluation, Tinetti Performance-Oriented Assessment of Mobility (POMA) for mobility evaluation. Mini Nutritional Assessment (MNA) was performed in all patients to detect nutritional status. If the total MNA score was \u0026lt;\u0026thinsp;17, the patient was categorized as malnourished. Depression was diagnosed using the geriatric depression scale-15 (GDS-15). A score of \u0026ge;\u0026thinsp;5 on the GDS-15 was considered as depression [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Calf circumference was assessed in sitting or supine position. For individuals in sitting position, measurements were taken on a chair in 90\u0026deg;-knee flexion with feet resting on the floor or on the footrest in a wheelchair. In the supine position, the knee joint was flexed at 90\u0026deg; with the feet and ankles relaxed. The flexible tape was wrapped perpendicular around the leg axis without pressing the tissue. Measurement was taken at maximum circumference [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDynapenia\u003c/strong\u003e \u003cp\u003eHandgrip strength was assessed three times on each hand using the Jamar hand-held hydraulic dynamometer (Jamar hand dynamometer; Sammons Preston, Inc., Bolingbrook, IL, USA). Handle width was adjusted to hand size. Individuals were standing with their arms parallel to their trunk and were encouraged to squeeze the dynamometer as hard as possible. The maximal handgrip strength was recorded. A maximal handgrip strength of \u0026lt;\u0026thinsp;27 kg for males was accepted as dynapenia [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Laboratory findings\u003c/h2\u003e \u003cp\u003eLaboratory tests were performed to evaluate inflammatory markers, the biochemical, metabolic, and nutritional status of the patients included complete blood count, kidney and liver functions, thyroid stimulating hormone, HbA1c and iron levels, iron-binding capacity (IBC), ferritin, vitamin B12, folic acid and vitamin D (25-hydroxy D3). Creatinine clearance from the kidney was estimated by the glomerular filtration rate (GFR) calculated using the chronic Renal Disease Epidemiology Collaborative (CKD-EPI) equation. Chronic Renal Failure (CRF) is defined as kidney damage or estimated GFR below 60 ml/min/1.73 m2.\u003c/p\u003e \u003cp\u003eAnemia was defined as hemoglobin concentrations below 13 g/dL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Statistical analyses\u003c/h2\u003e \u003cp\u003eDescriptive statistics of qualitative variables are presented as numbers and percentages, and the descriptive statistics of the quantitative variables are presented as mean, standard deviation, median, minimum, and maximum. The conformity of the quantitative variables to the normal distribution was evaluated with the Kolmogorov Smirnov test. The Mann Whitney U test was used to compare the mean of two independent groups. Pearson chi-square analysis was used for comparisons between the groups in terms of the ratios of the relevant qualitative variables. Logistic regression analysis was used to evaluate the relationships between the dependent variable and the independent variables. Enter method was used as variable selection method. The statistical significance level was taken as two-sided P\u0026thinsp;\u0026le;\u0026thinsp;0.05, and the SPSS (version 26.0; IBM Corp, Armonk, NY, USA) package program was used for analyses. It was calculated that at least 198 older male patients needed to participate in the study with a 5% margin of error and a 95% confidence interval.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eOf the 223 older male patients, 43.9% (n=98) had anemia. The mean age of the patients was 80.17\u0026plusmn;7.69 years. Patient characteristics, comorbidities, laboratory findings and geriatric syndromes/CGA parameters are summarized in \u003cstrong\u003eTable 1.\u003c/strong\u003e A significant difference was observed between the anemic and non-anemic groups in terms of the presence of DM, CKD and CHF (p \u0026lt;0.05). There was no difference between the two groups in terms of education, age and other comorbidities (p\u0026gt;0.05) (Table 1).\u003c/p\u003e\n\u003cp\u003eNumerous laboratory parameters differed between groups with and without anemia. While MCV, iron, IBC and GFR were lower in the group with anemia, red cell distribution width were higher. All CGA parameters were more negatively affected, except for MMSE, and geriatric syndromes were more common in patients with anemia compared to those without anemia (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e shows that after adjusting for age, in those with anemia compared to those without, adverse effects on malnutrition, dynapenia, BADL, IADL, and GDS scores were statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05)\u0026nbsp;(Model 2). In Model 3 multivariate analysis, adjustment was made according to age,\u0026nbsp;DM, CHF, and CKD. \u0026nbsp;BADL [OR: 0.95 (95% CI 0.93\u0026ndash;0.98)], IADL [OR: 0.91 (95% CI: 0.87\u0026ndash;0.97)], dynapenia [OR: 3.44 (95% CI: 1.78\u0026ndash;6.66)], and malnutrition [OR: 4.07 (95% CI: 1.14\u0026ndash;11.58)] scores were statistically significant (p \u0026lt; 0.05).\u0026nbsp;In Model 4, in addition to the confounders in Model 3, GDS and malnutrition were added to the adjustment, and the significant association of anemia with deterioration in BADL and IADL scores remained (p \u0026lt; 0.05) (see Table 2). However, after adjustment Model 4+ Dynapenia, there was no significant relationship between anemia and ADL\u0026rsquo;s.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e shows that after adjusting for age,\u0026nbsp;DM, CHF and CKD, in those with anemia compared to those without, adverse effects on feeding [OR: 2.74 (95% CI: 1.18\u0026ndash;6.36)], bathing [OR: 1.34 (95% CI: 1.01\u0026ndash;1.76)], dressing [OR: 1.57 (95% CI: 1.02\u0026ndash;2.42)], mobility [OR: 0.95 (95% CI: 0.91\u0026ndash;0.98)], and stair climbing [OR: 1.49 (95% CI: 1.13\u0026ndash;1.97)], scores were statistically significant (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt; 0.05)\u0026nbsp;(Model 1). In Model 2, in addition to the confounders in Model 1, GDS and malnutrition were added to the adjustment, and significant associations were observed between anemia with mobility [OR: 1.84 (95% CI: 1.28\u0026ndash;2.64)], and stair climbing [OR: 1.36 (95% CI: 1.02\u0026ndash;1.81)] (p \u0026lt; 0.05). After adding dynapenia to the model, no significant relationship remained between anemia and each item of BADL\u0026rsquo;s.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e shows that after adjusting for age,\u0026nbsp;DM, CHF and CKD, in those with anemia compared to those with no anemia, adverse effects on shopping [OR: 1.23 (95% CI: 1.02\u0026ndash;1.43)], \u0026nbsp;food preparation [OR: 1.29 (95% CI: 1.08\u0026ndash;1.53)], housekeeping [OR: 1.61 (95% CI: 1.08\u0026ndash;2.41)] and mode of transportation [OR: 1.31 (95% CI: 1.10\u0026ndash;1.55)] scores were statistically significant (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt; 0.05) (Model 1). In Model 2, in addition to the confounders in Model 1, GDS and malnutrition were added to the adjustment, and the significant association of anemia with shopping [OR: 1.18 (95% CI: 1.00\u0026ndash;1.38)], food preparation [OR: 1.22 (95% CI: 1.02\u0026ndash;1.46)] and mode of transportation [OR: 1.25 (95% CI: 1.05\u0026ndash;1.49)] remained. After adding dynapenia, there was no significant relationship between anemia and each item of IADL\u0026rsquo;s.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study investigated\u0026nbsp;the relationship between anemia and basic and instrumental activities of daily living in older male patients. The frequency of DM, CHF, and CKD was higher in those with anemia than those without anemia. Among geriatric syndromes, depression, malnutrition and dynapenia were more common in anemic patients. Dependence on ADLs was higher in older men with anemia than in those without. However, this significant difference did not persist after adjustment for geriatric syndromes, especially dynapenia, that may affect this dependence.\u003c/p\u003e\n\u003cp\u003eIn older adults, anemia has multiple causes and is typically linked to socio-demographic characteristics, lifestyle choices, and chronic conditions including CKD, DM, and CVD, as well as deficiencies in nutrients such as iron, vitamin B12, and folate [30-32]. Nevertheless, in approximately 14% to 50% of elderly individuals, the underlying cause of anemia remains unidentified despite extensive examinations [6,32]. In the current study, we observed anemia (Hb level below 13 g/dl) in 98 (43.9%) of 223 patients. This prevalence value, independent of the etiology, is higher than the prevalence data obtained from other studies. Research findings on anemia prevalence in older men have shown varying results. In one study, Stauder et al. reported that 11% of elderly males were affected by anemia [33]. Conversely, a different investigation conducted by Awaluddin et al. discovered a higher prevalence rate of 30.7% among older men [34]. The observed differences could be attributed to several factors, including the older average age of our study population, as well as variations in racial and ethnic backgrounds, economic status, food preferences, and coexisting medical conditions. Conversely, research by Chan et al. revealed that anemia was present in 70.5% of elderly male residents in nursing homes [35]. This high prevalence can be attributed to several factors characteristic of this patient population, including reduced functional abilities, increased occurrence of frailty, and a higher incidence of additional health issues and geriatric conditions such as malnutrition.\u003c/p\u003e\n\u003cp\u003eIn present study, anemia in older men was found to be associated with DM, HT, CAD, and CKD. The relationship between these comorbid diseases and anemia and their possible mechanisms have previously been identified; thus, our results support these findings. A research study conducted by Michalak et al., involving 981 participants, revealed that 24.9% of patients were diagnosed with DM. Additionally, within the same investigation, 23.8% of a subgroup consisting of 105 elderly male subjects exhibited both anemia and DM [36]. In our study, the rate of patients with anemia and DM was calculated to be 44.9%. Multiple factors contribute to the development of anemia in DM. These include ongoing inflammation, lack of essential nutrients, reduced renin production, coexisting autoimmune conditions, concurrent use of certain HT medications (especially angiotensin II receptor blockers) and \u0026nbsp; antihyperglycemic agents (particularly metformin), alterations in hormone levels, and impaired kidney function [37-38]. Additionally, men with type 2 DM frequently exhibit obesity, insulin resistance, and reduced testosterone levels, which could potentially elevate their risk of developing anemia [39]. In the presence of chronic kidney disease (CKD), erythropoietin production is impaired, leading to a primary hematologic manifestation characterized by severe hypoproliferative anemia [40]. Consequently, anemia may contribute to the advancement of chronic kidney disease, higher mortality rates, and a diminished quality of life. Since CKD is associated with geriatric syndromes that may negatively affect ADLs in the older adults, we adjusted for its effect in our study [41]. The same may also be true for anemia and CVD. The research conducted by Spazzafumo et al. revealed a link between anemia and increased cardiovascular risk [42]. Therefore, simultaneous treatment of anemia may be an important element of the management of these diseases.\u003c/p\u003e\n\u003cp\u003eIn the present study, we found that the dependence in both basic and instrumental life activities is more common in older men with anemia. This finding is consistent with previous studies. Research conducted by Maraldi et al. revealed that anemic males had a higher likelihood of experiencing impaired physical function and disability, with the risk increasing by a factor of 1.7 [43]. According to Maraldi et al., the inclusion of demographic and lifestyle factors in multivariate analysis only slightly reduced the strength of association. However, when nutritional factors and disease-related variables were considered, they observed a more substantial decrease in the strength of association. Consistent with previous research, this investigation revealed a strong correlation between anemia and dependency. However, when factors such as comorbidities, geriatric depression, and nutritional status were controlled for, the strength of this relationship decreased, though it remained statistically significant.\u0026nbsp;However, we also evaluated the effect of dynapenia on this relationship, and showed that the connection between ADLs and anemia is largely due to dynapenia. Therefore, there is clear importance of anemia-related muscle weakness in an elderly male patient in maintaining independence in activities of daily living. Notably, when dynapenia and anemia occur together, they are strongly linked to an increased likelihood of death from any cause over a 10-year follow-up period. This association remains significant even after accounting for socioeconomic factors, lifestyle choices, and existing health conditions [44]. Anemia\u0026apos;s impact on reducing oxygen delivery to tissues also impacts musculoskeletal structures, which may explain the diminished strength and muscle performance observed in anemic individuals [45]. These findings regarding anemia\u0026apos;s effect on functional capacity clearly suggest a significant role of dynapenia [18].\u003c/p\u003e\n\u003cp\u003eOne of the strengths of this study is the adequate sample size of patients with anemia. Another strength is that anemia screening and comprehensive geriatric evaluation were performed on the same day. A final strength is that only older men were included in the study; thus, sex-related effects could be excluded. Several limitations of this study should be considered when interpreting findings. Firstly, anemic men were not grouped among themselves according to the severity of anemia and were evaluated only at one visit. Second, erythropoietin levels were not routinely checked in all patients, which is important in deciding whether the anemia is transient or permanent. Another limitation of the study is that functional iron deficiency (transferrin saturation \u0026lt;20%, ferritin \u0026gt;100 ng/ml) was not examined in detail. Finally, the study utilized a cross-sectional design and thus direction of the observed association cannot be established it is possible that the relationship is bi-directional, for example, dependence in daily living may lead to malnutrition that subsequently leads to anemia. Future studies utilizing a longitudinal design are now required to elucidate on the direction of the association.\u003c/p\u003e\n\u003cp\u003eIn conclusion, approximately one in every two older men presenting to a Turkish outpatient clinic had anemia. Anemic men were older and had a higher incidence of DM, HT, CKD, malnutrition, geriatric depression and dynapenia. Anemia is associated with dependence in both basic and instrumental activities of daily living. However, dynapenia has an important contribution to this association. Therefore, older men should routinely be tested for anemia, anemia related reduced muscle strength should be investigated and treated in order to prevent dependency on daily life activities.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eConflict of interest\u003c/strong\u003e \u003cp\u003eNone.\u003c/b\u003e \u003ch2\u003eEthical approval\u003c/strong\u003e \u003cp\u003e The study design and all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee of Bezmialem Vakif University\u0026mdash;14/300) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e \u003ch2\u003eHuman and animal rights disclosure\u003c/h2\u003e \u003cp\u003eThis article does not contain any studies with animals performed by any of the authors.\u003c/p\u003e \u003ch2\u003eInformed consent\u003c/h2\u003e \u003cp\u003e Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003ch2\u003eAuthor details\u003c/h2\u003e \u003cp\u003e1 Department of Hematology, University of Health Sciences, Istanbul Training and Research Hospital, İstanbul, Turkiye. 2 Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkiye. 3 Department of Hematology, Biruni University Faculty of Medicine, Biruni University Hospital, Istanbul, Turkiye. 4 Department of Hematology, University of Health Sciences, Istanbul Basaksehir Cam and Sakura City Hospital, Istanbul, Turkiye. 5 Department of Hematology, Istinye University Faculty of Medicine, Liv Hospital, Istanbul, Turkiye. 6 Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran. 7 Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea. 8 Centre for Health Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding was provided for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDesign study: Abdulkadir KARISMAZ; practical performance: Abdulkadir KARISMAZ, Rafet EREN; data analysis: Pinar SOYSAL Istemi SERIN; preparation manuscript: Abdulkadir KARISMAZ, Dong Keon YON; critical review manuscript: Lee SMITH, Masoud RAHMATI. All authors contributed to the draft and revision of the manuscript and approved the version to be published.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors would like to acknowledge the participants.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe datasets used and analyzed during the current study will be made available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePenninx BWJH, Pahor M, Woodman RC, Guralnik JM (2006) Anemia in old age is associated with increased mortality and hospitalization. J Gerontol Biol Sci Med Sci 61:474\u0026ndash;479\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCulleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR (2006) Impact of anemia on hospitalization and mortality in older adults. 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Aging Clin Exp Res 18(6):485\u0026ndash;492\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang Z, Han X, Wang Y et al (2022) Red cell distribution width, anemia, and lower-extremity physical function among rural-dwelling older adults. Aging Clin Exp Res 34(10):2483\u0026ndash;2491\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerna S, Peroni G, Faliva MA et al (2017) Sarcopenia and sarcopenic obesity in comparison: prevalence, metabolic profile, and key differences. A cross-sectional study in Italian hospitalized elderly. Aging Clin Exp Res 29(6):1259\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuiz MM, Schneider IJC, Kuriki HU et al (2022 Sep-Oct) The combined effect of anemia and dynapenia on mortality risk in older adults: 10-Year evidence from the ELSA cohort study. Arch Gerontol Geriatr 102:104739\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDodd SL, Powers SK, Brooks E, Crawford MP (1993) Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle. J Appl Physiol 74(1):186\u0026ndash;191\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHammer T, Braisch U, Rothenbacher D, Denkinger M, Dallmeier D (2024) Relationship between hemoglobin and grip strength in older adults: the ActiFE study. Aging Clin Exp Res 36(1):59\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"aging-clinical-and-experimental-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"acer","sideBox":"Learn more about [Aging Clinical and Experimental Research](http://link.springer.com/journal/40520)","snPcode":"40520","submissionUrl":"https://submission.nature.com/new-submission/40520/3","title":"Aging Clinical and Experimental Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"older men, anemia, activities of daily living, dynapenia","lastPublishedDoi":"10.21203/rs.3.rs-5053902/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5053902/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eThe aim of the present study was to examine the relationship between anemia and basic and instrumental activities of daily living in older male patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 223 older males attending one geriatric outpatient clinic were included in this cross-sectional study. Anemia was defined as a hemoglobin level below 13 g/dL. Patients' demographic characteristics, comorbidities, and comprehensive geriatric assessment parameters were also recorded. Handgrip strength of \u0026lt;\u0026thinsp;27 kg for males was accepted as dynapenia. Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) questionnaires were used to evaluate functional capacity.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean age (standard deviation) of the participants was 80.17 (7.69) years. The prevalence of patients with anemia was 43.9%. There was differences between anemic and non-anemic groups in terms of presence of diabetes mellitus (DM), congestive heart failure (CHF), chronic kidney disease (CKD), malnutrition, dynapenia, geriatric depression, BADL and IADL scores (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In multivariate analysis, after adjusting for all confounding variables except for dynapenia, patients with anemia were associated with reduced BADL and IADL (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). After adjusting for all confounding variables including dynapenia, deterioration in total BADL and IADL scores did not remain significant in the anemic group compared to the non-anemic group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eClose to one in two older outpatient men had anemia. Anemic men had a higher incidence of DM, CHF, CKD, malnutrition, geriatric depression and dynapenia. Anemia was associated with dependence in both BADL and IADL in older men. However, comorbidities, nutritional status, depressive mood and, specifically muscle strength, were important contributors to this association.\u003c/p\u003e","manuscriptTitle":"The Connection Between Anemia and Limitations in Daily Activities Among Older Males: The Critical Role of Dynapenia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-16 05:23:08","doi":"10.21203/rs.3.rs-5053902/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-14T19:11:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-14T18:53:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-09T22:06:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256022001808741741976744984891427301916","date":"2024-09-09T17:38:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140580141763694099983340874467024126876","date":"2024-09-09T11:22:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-09T10:52:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-09T09:30:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-09T07:13:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Aging Clinical and Experimental Research","date":"2024-09-08T18:43:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"aging-clinical-and-experimental-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"acer","sideBox":"Learn more about [Aging Clinical and Experimental Research](http://link.springer.com/journal/40520)","snPcode":"40520","submissionUrl":"https://submission.nature.com/new-submission/40520/3","title":"Aging Clinical and Experimental Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"88d33e3b-5dc9-4979-ace3-48a5b0e036b2","owner":[],"postedDate":"October 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T15:59:22+00:00","versionOfRecord":{"articleIdentity":"rs-5053902","link":"https://doi.org/10.1007/s40520-024-02859-8","journal":{"identity":"aging-clinical-and-experimental-research","isVorOnly":false,"title":"Aging Clinical and Experimental Research"},"publishedOn":"2024-10-26 15:57:05","publishedOnDateReadable":"October 26th, 2024"},"versionCreatedAt":"2024-10-16 05:23:08","video":"","vorDoi":"10.1007/s40520-024-02859-8","vorDoiUrl":"https://doi.org/10.1007/s40520-024-02859-8","workflowStages":[]},"version":"v1","identity":"rs-5053902","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5053902","identity":"rs-5053902","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}