Background: Anemia in the elderly is common and may be associated with atypical clinical presentations. Although the impact of severe anemia on cognition has been studied in patients with cancer, less is known about the association of mild anemia on cognitive function in the elderly. Executive cognitive functioning (ECF) refers to the execution of complex activities that involve a set of higher-order cognitive abilities primarily dependent on the frontal lobes. ECF plays a major role in the maintenance of the functional status of older adults. Knowledge about potentially modifiable risk factors for ECF impairment in older adults is limited. The goal of this study was to test the hypothesis that mild anemia is associated with ECF impairment in high functioning, community-dwelling older women.

Methods: Cross-sectional analysis of baseline data from the Women’s Health and Aging Study (WHAS) II, 1994–1996, Baltimore, MD. WHAS II is a population-based study of 436 cognitively intact (Mini-Mental State Exam >24) and highly physically functioning women aged 70–80 years. The analytic sample included 364 subjects with Hb >10 g/dL and the following ECF test components: Trail Making Tests part B (TMTB) - primary outcome - and part A (TMTA), and the difference TMTB-TMTA. Multivariate polytomous logistic regression models were used to model the relationship between performance (based on tertiles) on each ECF test as a function of Hb, while controlling for age, education, cardiovascular disease, and a number of other potential confounders, such as hypertension, diabetes, depressive symptoms, calculated creatinine clearance, forced expiratory volume in the first second, thyroid stimulating hormone, total cholesterol levels, body mass index, walking speed, and prevalent mobility difficulty.

Results: Subjects with mild anemia (Hb 10–12 g/dL) performed worst in all ECF tests; i.e., the percentage of subjects in the best performance tertile for each test was lowest for those with Hb within 10–12 g/dL. Estimates from multivariate models revealed that, as compared to those with Hb≥12 g/dL, those with Hb within 10–12 g/dL were substantially less likely to be in the best performance tertile of the TMTB [odds ratio (OR).23, 95% confidence interval (CI):.06–.86; p=.029], TMTA (OR.27, 95%CI:.07–.98; p=.047), and TMTB-TMTA (OR.30, 95%CI:.10–.89; p=.031), even after comprehensive adjustment.

Conclusion: In this cross-sectional study, mild anemia was an independent risk factor for prevalent ECF impairment in high functioning community-dwelling older women. This raises the hypothesis that correction of mild anemia could potentially provide an opportunity for prevention of cognitive and functional decline in older adults. To test this hypothesis, prospective observational studies and clinical trials are warranted.

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