Association Between Mild Anemia and Physical and Mental Impairments in the Elderly

Studies show that hemoglobin (Hb) levels progressively decline, as part of the aging process, leading to Hb levels in most elderly persons that are slightly lower than the lower limit of normal. Although anemia is viewed by most physicians as having no clinical significance and no independent effect on health, it has been shown to be associated with a number of health indicators. Several cross-sectional studies have found an association of anemia with a variety of physical and health issues in elderly persons. Some of these findings include diminished physical performance and muscular strength and increased risk of frailty and fall injury events.

In a prior study of elderly persons (65+) conducted in Italy, researchers found that the prevalence for dementia, cognitive impairment, functional disability, and health problems was greater in the oldest members of the elderly population. These findings prompted the authors to separate the population into a younger (65-84 years old) and older (85 +) cohort. The study described below, Health and Anemia, is an observational study of the younger cohort (65-84 years old) to determine the prevalence of dementia, cognitive impairment, functional disability, and health problems.

The objective of this cross-sectional study was to investigate the association of mild anemia with cognitive, functional, mood, and quality of life variables, using the Geriatric Depression Scale-10, Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia.

The study population was based on older individuals residing in the municipality of Biella, Piedmont, Italy on May 12, 2003. Among the 10,110 community dwelling residents, factors consisting of death, inability to contact, and refusal or inability to participate, resulted in a remainder of 4,501 individuals who agreed to take part in the study. Exclusion criteria led to a total study population of 547 non-anemic persons and 170 mild anemic persons. Mild grade anemia was defined as an Hb concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Individuals with a Hb concentration below 10 g/dL were excluded. Possible differences based on demographic and clinical characteristics were controlled by comparing the study population to individuals, not included in the study. Univariate analyses and multivariable adjusted regressions were used to determine associations.

Results on almost all cognitive, functional, mood, and quality-of-life measures were significantly worse in mild anemic elderly persons. After controlling for various demographic and clinical confounders, analysis by multivariable logistic regression found mild anemia to be significantly associated with measures of selective attention and disease-specific quality-of-life measures (all fully adjusted p=0.046). Using the lower limit of normal Hb concentration according to WHO criteria, differences between mild anemic and non-anemic elderly persons tended to be increased on almost every variable. Results of the study are especially important, since mild anemia is typically overlooked in the elderly. Further studies using longitudinal and clinical trial designs would further increase our knowledge of potential risks of mild anemia in the elderly.

Please reference the source article:
Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the "Health and Anemia" study. Lucca U, Tettamanti M, Mosconi P, Apolone G, Gandini F, Nobili A, Tallone MV, Detoma P, Giacomin A, Clerico M, Tempia P, Guala A, Fasolo G, Riva E. PLoS ONE. 2008;3(4):e1920.

NAAC Expert Commentary:
This cross-sectional study analyzed the impact of mild anemia on cognition, function, and quality of life among Italians from 65-84 years of age. The authors report that the presence of anemia showed an adverse association with most outcomes. Although statistical adjustment negated many of these associations, the adverse impact of anemia on disease-related quality of life persisted.

The limitations of cross-sectional association studies are well appreciated. Beyond this, methodology problems hinder drawing conclusions in this study. The excessive number of outcomes and multiple covariates used in adjustment runs the risk of both false negative and false positive findings. The statistical evaluation would also have benefited from interrogating hemoglobin (Hb) in 1 g/dL categories and assessing for trends. Data on Hb concentrations where outcomes are best (i.e. best quality of life or least functional impairment) provides insight into optimal Hb values.

Despite these limitations, the data reported herein are remarkably consistent to other published data. Prior studies on cognition and anemia have generally not been able to demonstrate an independent association between anemia and diminished cognition. Although not emphasized by the authors, the association of anemia to reduced quality of life in the physical aspects but not emotional components of the instruments may have been the most intriguing finding. This supports the concept that mild anemia could directly cause functional impairments and fatigue through reduced muscle oxygenation.

Celiac Disease as Potential Cause of Iron Deficiency in Older Adults

Iron deficiency anemia occurs when the total iron body content falls to insufficient levels that cause inadequate erythropoiesis and subsequent development of anemia. However, in 50% of elderly persons with iron deficient anemia, no source of iron loss can be identified. The authors of the article described below have suggested that the iron-loss in these patients may be due to an unsuspected cause: Celiac disease.

The diagnosis and perception of celiac disease (CD) has drastically changed over the last twenty years. Once a primarily pediatric condition, more CD cases with a myriad of symptoms are now being reported in elderly populations. However, CD diagnoses in elderly patients commonly occur long after the onset of symptoms, which can lead to a diminished quality of life and reduced longevity. A recent study described several cases of CD in these patients to evaluate the range of symptoms and potential treatment options.

The study examined retrospective charts of 7 patients (3 male and 4 female) 60 years of age or older. CD was diagnosed by compatible histological findings. Symptoms, duration of symptoms, celiac serology evaluation, and response to a gluten-free diet were recorded from patient charts. Also, 6 patients were given follow-up interviews concerning family history, duration and type of symptoms, and response to the gluten-free diet.

The most frequent presenting symptoms were weight loss (4 patients) and iron deficiency anemia (5 patients). Also, patients experienced abdominal pain, diarrhea, elevated liver transaminases, and severe osteoporosis. One patient had a history of peripheral neuropathy, as well as folic acid deficiency. In most patients, lag diagnosis of CD (median duration of 8 years) was significant. Despite the variety and severity of symptoms in the study population, initiation of a gluten-free diet resulted in a complete resolution of symptoms and significant weight gain in 6 patients. In addition, significant improvements were seen in two female patients with longstanding cognitive decline.

Similar to this study, other clinical trials have reported that elderly patients comprise up to 25% of new CD cases. However, the lag of CD diagnosis is still unacceptably long, since many symptoms are attributed to old age and decreased cognitive abilities in these patients. More clinical trials are needed to determine whether CD progresses into a clinical condition from a subclinical condition that deveops from decreased body reserves or from other factors. Also, the link between cognitive decline and CD needs to be further explored. Although these associations are not well understood, the striking improvement of symptoms from gluten-free diets merits much more investigation into this patient population.

Please reference the source article:
Celiac disease diagnosed in the elderly. Lurie Y, Landau DA, Pfeffer J, Oren R. J Clin Gastroenterol. 2008;42(1):59-61.

NAAC Expert Commentary:
Approximately 15% of anemia found in older individuals is due to iron deficiency, yet in half of those cases, no source of iron loss is found. This puzzle has never been completely resolved: it has become clear that H. Pylori infections or copper deficiency may be a cause of iron deficiency in older individuals in rare occasions. This article proposes a new unsuspected cause of iron deficiency in older individuals. It demonstrates that celiac disease may be a cause of iron deficiency anemia in individuals aged 60 and over. The exact prevalence of celiac disease among older individuals is not known yet, but it should become part of the differential diagnosis of iron deficiency, especially if the iron deficiency is associated with otherwise unexplained weight loss.

References in the commentary:
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(7) Belonje AM, et al. Cardiovasc Drugs Ther 2008;22:1-2.
(8) Information for Healthcare Professionals Erythropoiesis Stimulating Agents (ESA). FDA. November 8, 2007.
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Obesity-related Hypoferremia Not Explained by Iron Intake or Absorption

Humans obtain dietary iron in two different forms: nonheme-associated iron and heme-associated iron. The two forms of iron are found predominantly in separate food sources, and are absorbed using separate pathways. The absorption of both heme- and nonheme- associated iron can be substantially altered by the co-consumption of certain dietary elements or foods.

Studies have shown that hypoferremia and iron deficiency are more prevalent in obese persons compared to nonobese persons. Researchers have hypothesized that this higher prevalence may be a result of differences between obese and nonobese persons in the (1) co-consumption of certain dietary factors or (2) co-consumption of different amounts of foods or vitamins containing heme- vs. nonheme- associated iron. To determine if these differences can explain the high prevalence of obesity-related hypoferremia, a cross-sectional study was conducted in a convenience sample of 207 obese and 177 nonobese adults during a 21-month period from April 2002 to December 2003.

The study compared the fasting blood iron, hemoglobin (Hb), transferrin, and ferritin between healthy overweight adults (body mass index of >/= 25 .0) and healthy normal weight adults (body mass index of 18.0 to 24.9). Participants were asked to complete a 7-day food record, which analyzed dietary iron intake using the Nutritional Data System for Research Software. Food groups were assessed for dietary iron content based on the USDA National Nutrient Database for Standard Reference Release No. 18.

The presence of hypoferremia was significantly greater in obese compared to nonobese adults (21.1% [95% confidence interval: 10.1% to 20.6%] vs. 14.6% [95% confidence interval: 19.7% to 31.5%]: P less than 0.05). Mean serum iron was lower among obese subjects (72.0 +/- 61.7 vs. 85.3 +/- 58.1ug/dL [12.888+/- 11.0443 vs. 15.2687+/-10.3999 umol/L]; P less than 0.001).

After accounting for demographic covariates and variables known to affect iron absorption, fat mass (ß =-0.330; P <0.05) remained a significant negative predictor of serum iron concentration. However, the only factor affecting dietary iron absorption was the percentage of calories from vegetable protein, which was a negative predictor for serum iron (P = 0.004). Small but insignificant differences were observed between obese and nonobese participants in the intake of nonheme iron and heme iron, as well as vitamin C and calcium.

The data suggests that obesity-related hypoferremia is not explained by differences in reported intake of iron or dietary factors that can affect iron absorption. The authors reported several limitations to the study, including potential problems associated with the self-reporting of food consumption and the potential for non-habitual iron intake during the study. Based on these results, more studies are necessary.

Please reference the source article:
Obesity-related hypoferremia is not explained by differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption. Menzie CM, Yanoff LB, Denkinger BI, McHugh T, Sebring NG, Calis KA, Yanovski JA. J Am Diet Assoc. 2008;108(1):145-8.

NAAC Expert Commentary:
The authors conclude that "obesity-related hypoferremia is not associated with differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption." The study attempted to adjust for non-obesity related variables, and seems to suggest that obesity-related physiologic factors, here to fore not described, may be at work.

Many practicing physicians have encountered these same difficulties in their attempts to correct obesity-related hypoferremia; a controlled study to confirm this anecdotal experience is intriguing. As the bariatric surgery post-op population grows, many physicians are recognizing the challenge that some patients in this group face when attempting to overcome hypoferremia. This study is helpful in moving toward a better understanding of this question. We can look forward to expanding the database in this area.