Is Low Hemoglobin Concentration Highly Associated with the Onset of Cognitive Impairment in Elderly People?

To the Editor

Recently, we read with great interest the article entitled “Low hemoglobin levels and the onset of cognitive impairment in older people: the PRO.V.A. study” by Trevisan et al., ¹ in which the authors conclude that low levels of hemoglobin are highly related to the onset of cognitive impairment in the elderly since a great limitation of oxygenation is induced by low hemoglobin concentration, which could not provide sufficient oxygen for peripheral tissues and the brain. We do not totally agree with this conclusion, and would like to bring forward our opinion in this letter.

Adequate hemoglobin carrying enough oxygen guarantees proper physiological functioning. ^2,3 Accumulating evidence suggests that sufficient oxygen for brain tissues may benefit a lot to the neurological and psychiatric symptoms. ⁴ This is only a necessary condition, rather than a decisive one. Interestingly, a cross-sectional study by Kurella et al. ⁵ enrolling 19,701 U.S. adults demonstrates that there is no significant association between the levels of hemoglobin and cognitive impairment. Clinically, severe shock caused by acute massive hemorrhage could induce an unexpected vicious result that patients may lose their lives without any effective means except for massive blood transfusion under this terrible condition. ⁶ Most of patients in this case may present cognitive impairment and even coma. ⁷ Nevertheless, chronic anemia resulting in loss of hemoglobin fails to induce cognitive impairment owing to long-term endurance of hypoxia by self-regulation. Furthermore, for chronic anemia, hemoglobin is gradually adapted to hypoxia through increase of the capacity to carry oxygen. ⁸ Obviously, the subjects enrolled in this study by Trevisan et al. ¹ are in a chronic anoxic condition, but not in a state of acute anoxia. It is, therefore, likely that subjects could well tolerate chronic anoxia through increasing hemoglobin's capacity to capture oxygen during a follow-up long period of 4.4 years. Possibly, it is an imperfect conclusion that low levels of hemoglobin elicit deficits of tissue oxygen delivery and, as a result, induce cognitive impairment.

The lifespan of normal red blood cells is ∼120 days. ^9,10 About 1/120 of red blood cells is replaced by the newborn cells. ¹¹ As shown in this study, the authors observe cognitive performances of individuals 4.4 years after initiation of measuring hemoglobin levels as an original baseline. We think that hemoglobin may fail to act as a biomarker to predict the onset of cognitive impairment in that it is probably varied markedly during the period of 4.4 years, which is much longer than red blood cells' lifespan. In addition, if low levels of hemoglobin are highly associated with cognitive impairment, transfusion of red blood cells may exert a beneficial effect. It is obvious, however, that there is no study that reports red blood cell transfusion greatly contributes to the treatment of cognitive impairment.

In conclusion, we maintain an opinion that low levels of hemoglobin are probably not related to the onset of cognitive impairment in elderly people, at least not a major cause. Further studies are required to find available biomarkers to better predict the onset of cognitive impairment in elderly.