This study investigated the relationship between anemia and basic and instrumental activities of daily living in older female patients. The frequency of DM, HT, CAD, and CKD was higher in those with anemia than those without anemia. Among geriatric syndromes, depression, malnutrition, dynapenia, and cognitive impairment were more common in anemic patients. Dependence on ADLs was higher in older women with anemia than in those without. Moreover, this significant difference persisted after adjusted for the geriatric syndromes that could affect this dependence [10, 22].
Anemia in the older adults is multifactorial and is often caused by suppression of erythropoiesis due to chronic inflammation (infection, malignancy, inflammatory diseases, etc.) and nutritional deficiencies (iron, vitamin B12, and folate) [23]. However, despite all investigations, the cause of anemia cannot be determined in approximately 14% to 50% of older adults [23-24]. In the current study, we observed anemia (Hb level below 12 g/dl) in 190 (35%) of 540 patients. This prevalence value, independent of the etiology, is higher than the prevalence data obtained from other studies. For example, Stauder et al. showed the prevalence of anemia to be 10.2% in older women [4]. In another study, Semba et al. found that the prevalence of anemia was 21.4% in older women [26]. This may be related to the higher mean age of our patient group, as well as race, ethnicity, and comorbid diseases. On the other hand, Sahin et al. showed the prevalence of anemia was 58.3% in nursing homes among older women [27]. This rate is higher than our study finding, which may be explained by lower functional capacities of patients in nursing homes or more common accompanying comorbid diseases and geriatric syndromes such as malnutrition that is a leading cause of anemia. Indeed, in their review, Beghe et al. revealed that the prevalence of anemia among geriatric women ranges between 3.3% to 41% [28]. This variability may be related to several factors, including the study setting, the health status of the population in question, and the criteria used to define anemia.
In our study, anemia in older women was found to be associated with DM, HT, CAD, and CKD. Indeed, DM and anemia are common conditions in older adults, and have been found to be associated with an increased level of severity of multiple comorbidities (e.g., cardiovascular diseases) as well as an increase in risk of mortality [29]. Overtime DM may lead to micro and macrovascular damage, which may have an adverse impact on the circulatory system, nervous system, kidneys, and eyes. Anemia is known to increase these complications in older diabetic patients [29]. In a study of 981 patients, Michalak et al. found the rate of patients with a diagnosis of DM to be 24.9%. In the same study, among 145 older women, 20% of patients had both anemia and DM[29]. In our study, the rate of patients with anemia and DM was calculated to be 42.6%. Differences in the frequency of coexistence of anemia and DM may be due to several factors. Current literature suggests that the coexistence of anemia and DM is commonly observed in patients who are hospitalized or under the care of specialized clinics. The level of health care, age (as the prevalence of anemia and DM increases with age), the economic situation of the country in which the study was conducted, and the geographical location (altitude) are also of importance. The etiology of anemia in DM may be owing to several key factors, including chronic inflammation, nutritional deficiencies, concomitant autoimmune diseases, concurrent HT medication (particularly, angiotensin II receptor blockers) and antihyperglycemic agents (notably, metformin), hormonal changes, and kidney disease [30-31]. In the presence of CKD, erythropoietin production is impaired and a severe hypoproliferative anemia dominates the hematologic picture [32]. In turn, anemia can lead to CKD progression, increased mortality and decreased 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 [33]. The same may also be true for anemia and cardiovascular disease. Culleton et al. demonstrated the association between anemia and cardiovascular risk. According to this study, the risk of CAD, HT and congestive heart failure is 3 to 4 times higher in the older patients with anemia [34]. Therefore, simultaneous treatment of anemia may be an important element of the management of these diseases.
In our study, we found that the dependence in both basic and instrumental life activities is more common in older women with anemia. This finding is consistent with previous studies. For example, Penninx et al. found that anemia was associated with disability and decreased physical performance in older adults [10]. Moreover, just as in our study, this study showed that muscle strength is decreased in patients with anemia. However, in this study, the effect of dynapenia (decreased muscle strength) on ADLs was not eliminated, and malnutrition was not evaluated as an etiological factor of anemia [10]. Jia et al. found that anemia was significantly associated with ADLs in older Chinese females [35]. In this study, only the relationship between basic activities of daily living and anemia was examined, whereas the present study demonstrates that instrumental activities are also negatively affected by anemia. These findings suggest that lower Hb levels are associated with greater daily living activity dependence. This relationship can be associated with several possible underlying mechanisms. The impact of anemia on function and strength decline may be related to reduced muscle oxygenation [36]. Anemia-induced hypoxia is a crucial factor for cellular functions in all organs, particularly the brain and skeletal muscles, and this can result in any component of frailty, such as fatigue, weakness, depression, and impaired physical activity [22, 37-38].
Dynapenia is an important factor altering the functional capacity of the elderly and causing disability [39]. Importantly, in a study with 10-years of follow-up anemia with dynapenia was associated with higher all-cause mortality risk, independent of socioeconomic factors, health behaviors and comorbidities [40]. An association between low Hb levels and low muscle strength has previously been observed in cross-sectional studies [40]. Alexandre et al., found that anemia was associated with dynapenia in 1168 older Brazilian adults[41]. Cesari et al., in a sample of 909 older adults residing in Italy, found that those with anemia presented a weaker ankle extension strength compared to those without anemia[42]. Additionally, a recent study reported that anemia was associated with dynapenia in older women, but not in older men [22]. Decreased oxygen delivery due to low Hb levels results in chronic hypoxia. Indeed, it is possible that chronic hypoxia may damage the musculoskeletal system, reducing muscle strength and thus leading to dynapenia. In addition, anemia associated fatigue may also leas to dynapenia, as it fatigue is associated with low levels of physical activity and thus muscle disuse[43-44]. All of the above-mentioned findings relating to the impact of anemia on functionality show that it has a clear contribution to dynapenia. However, interestingly, we found that dependence in ADL (especially food preparation, climbing stairs, and transportation) was more common in older women with anemia, even after the confounding effect of dynapenia was adjusted for. This suggests that anemia may affect functionality not only through decreased muscle strength, but also through other mechanisms (eg, orthostatic hypotension or cerebral hypoperfusion).
There is also a close relationship between anemia, malnutrition and functionality. Ramel et al. demonstrated that anemia was correlated with biological (albumin, prealbumin, and lymphocyte count) and clinical (body mass index, weight loss, triceps skinfold thickness, mid-arm muscle circumference) parameters of malnutrition [45]. In our study, the prevalence of malnutrition was greater in patients with anemia. Particularly, the relationship between malnutrition and shopping and food preparation suggests that nutritional problems in the elderly may cause anemia. Moreover, our findings related to stair climbing in BADL, addiction in mobility and difficulties in transportation from IADLs may be associated with malnutrition sarcopenia [46]. Therefore, it is important to control for nutritional factors when assessing functionality.
A clear strength of this study includes the adequate sample size of patients with anemia. Moreover, it is advantageous that anemia screening and comprehensive geriatric evaluation were performed on the same day. A final strength is that only older women were included in the study; thus, sex-related effects were eliminated. Several limitations of this study should be considered. Firstly, those with anemia were not grouped according to the severity of the condition and were evaluated at single outpatient 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 <20%, ferritin >100 ng/ml) was not examined in detail. Finally, the study utilized a cross-sectional design and thus direction of associations cannot be established.
In conclusion, one out of every three older women presenting to a Turkish outpatient clinic had anemia. Anemic women were older and had a higher incidence of DM, HT, CAD and CKD as comorbid diseases. Anemia is associated with dependence in both basic and instrumental activities of daily living. Particularly, cognitive dysfunction, dynapenia and malnutrition contribute to this association. However, anemia is associated with decreased functionality and increased falls, which is independent of all these factors. Therefore, older women should routinely be tested for anemia, and possible causes should be investigated and treated in order to prevent these negative outcomes.