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BALTIMORE, Sept. 15 -- Mild anemia, long associated with to fatigue and weakness, may be an independent risk factor for loss of so-called executive function in older patients, researchers reported.

Community-dwelling women, ages 70 to 80, with anemia were four to five times more likely to perform poorly on executive function tests compared with those having normal hemoglobin levels, according to a study in the September issue of The Journal of the American Geriatrics Society.

Impaired executive function (ability to solve problems, plan, assess danger, track important activities) often precedes memory loss and may affect the ability to carry out daily-living activities, such as shopping, cooking, taking medications, paying bills, and walking, said Paulo Chaves, M.D., Ph.D., of Johns Hopkins here, and colleagues.

A number of studies have investigated the relationship between mild anemia and physical functioning in community-dwelling older patients, but cognition has lagged behind, he said.

Dr. Chaves and his team studied 364 high-functioning older women (mean age 73.9), participating in the Women's Health and Aging Study II, in Baltimore, from 1994 to 1996.

More than 80% of the women had a Mini-Mental State Examination score of 27 or greater, and the hemoglobin for most was in the normal range, with only 8.6% (n=30) with anemia, defined as Hb less than 12.0 g/dL.

Physical functioning for the participants was good for the participants, with more than half rating their health status as excellent or very good. All the subjects had a hemoglobin concentration of 10 g/dL or greater and known executive-function status at the outset.

The tests commonly used to evaluate executive function were Trail Making Test (TMT) Parts B and A. Tertiles of time to complete each test were used to define best, intermediate, and worst performance. Tertiles of the difference, TMT-B minus TMT-A, were calculated to rate the participants.

Analysis of the test results showed that those with anemia were four to five times more likely to perform worst on the executive function tests, compared with those with normal hemoglobin. Put another way, some 15% of those with the worst results on all three tests were anemic, compared with only 3% who scored best, the researchers said.

Prevalent anemia substantially increased the likelihood of performing worst (as opposed to best) on the TMT-B (odds ratio 5.2, 95% confidence interval 1.3-20.5), TMT-A (OR 4.8, CI 1.5-15.6), and TMT-B minus TMT-A (OR 4.2, CI 1.0-17.2). These scores were calculated after controlling for age, education, race, prevalent diseases, and relevant physiological and functional parameters.

The percentage of subjects in the best TMT-B performance tertile was lowest for hemoglobin levels of 10 g/dL to 11.9 g/dL, intermediate for Hb 12.0 g/dL to 12.9 g/dL, and highest for categories including Hb concentrations of 13 g/dL or greater.

Conversely, having an Hb of 13g/dL to 13.9 g/dL was associated with the lowest percentage of participants in the worst TMT-B performance groups, the researchers reported.

Whether the relationship between anemia and executive function is causal remains to be determined, the researchers said. A possible causal pathway for the anemia effect could involve chronic reduction of cerebral oxygenation secondary to decreased oxygen-carrying capacity of blood linked to anemia.

Another potential causal pathway, they suggested, could involve the negative effect of anemia on physical functioning and conditioning. Finally, they said, there is the possibility that anemia might be just a marker of diseases and processes associated with chronic cerebral hypoperfusion in the prefrontal cortex or neurodegenerative processes such as inflammation.

This study has several limitations, the researchers wrote. First, because of its cross-sectional nature, the risk of incident executive function impairment as a function of baseline anemia or change in Hb over time was not assessed.

Second, a few caveats about the operational definition used for executive function impairment should be acknowledged. The definition was based on only a few measures of executive abilities. Also, there is currently no well-established clinical criterion to define executive function impairment in older adults.

Other limitations included the possibility that positive confounding from unmeasured disease-related factors, such as subclinical cerebrovascular disease, might have affected the results.

The study's sample size was small, they noted, and the effect of different types of anemia on executive function was not assessed.

Finally, they said, only U.S. urban women, ages 70 to 80, who were high functioning and highly educated were assessed. Thus generalizability of the study is limited.

In summing up, Dr. Chaves said that study, which builds on the body of literature contributing novel data on mild anemia and impairment in a specific domain of cognitive function, is particularly relevant for community-dwelling older adults.

Though preliminary, the evidence supports the hypothesis that mild anemia might be an independent risk factor for impaired executive function in these older adults, he said, but added that the findings do not indicate that treatment of anemia would necessarily lead to improvement.

Further investigation through prospective epidemiological and experimental studies is warranted, the researchers wrote. The findings, Dr. Chaves added, "are compelling enough to serve as a roadmap for continued research."

Funding for this study included a research grant from Ortho Biotech Products, maker of Procrit (erythropoietin). Dr. Chaves wrote that he has served as a paid consultant to Ortho Biotech Products. The terms of the latter arrangement were managed by Johns Hopkins University in accordance with its conflict-of-interest policies.