Red blood cells

A population-based study conducted in Germany has suggested a link between anemia and mild cognitive impairment (MCI).

Researchers found that subjects with anemia, defined as hemoglobin <13 g/dL in men and <12 g/dL in women, performed worse on cognitive tests than their nonanemic peers.

And MCI occurred almost twice as often in subjects with anemia than in subjects with normal hemoglobin levels.

This study was published in the Journal of Alzheimer’s Disease.

About MCI

MCI represents an intermediate and possibly modifiable stage between normal cognitive aging and dementia. Although individuals with MCI have an increased risk of developing dementia or Alzheimer’s disease, they can also remain stable for many years or even revert to a cognitively normal state over time. This modifiable characteristic makes the concept of MCI a promising target in the prevention of dementia.

The following 4 criteria are used to diagnose MCI. First, subjects must report a decline in cognitive performance over the past 2 years. Second, they must show a cognitive impairment in objective cognitive tasks that is greater than one would expect taking their age and education into consideration.

Third, the impairment must not be as pronounced as in demented individuals since people with MCI can perform normal daily living activities or are only slightly impaired in carrying out complex instrumental functions. Fourth, the cognitive impairment has to be insufficient to fulfil criteria for dementia.

The concept of MCI distinguishes between amnestic MCI (aMCI) and non-amnestic MCI (naMCI). In the former, impairment in the memory domain is evident, most likely reflecting Alzheimer’s disease pathology. In the latter, impairment in non-memory domains is present, mainly reflecting vascular pathology but also frontotemporal dementia or dementia with Lewy bodies.

Study details

The Heinz Nixdorf Recall study is an observational, population-based, prospective study in which researchers examined 4814 subjects between 2000 and 2003. Subjects were 50 to 80 years of age and lived in the metropolitan Ruhr Area. Both genders were equally represented.

After 5 years, the researchers conducted a second examination with 92% of the subjects taking part. The publication includes cross-sectional results of the second examination.

First, 163 subjects with anemia and 3870 without anemia were included to compare their performance in all cognitive subtests.

The subjects took verbal memory tests, which were used to gauge immediate recall and delayed recall. They were also tested on executive functioning, which included problem-solving/speed of processing, verbal fluency, visual spatial organization, and the clock drawing test.

In the initial analysis, anemic subjects showed more pronounced cardiovascular risk profiles and lower cognitive performance in all administered cognitive subtests. After adjusting for age, anemic subjects showed a significantly lower performance in the immediate recall task (P=0.009) and the verbal fluency task (P=0.004).

Next, the researchers compared 579 subjects diagnosed with MCI—299 with aMCI and 280 with naMCI—to 1438 cognitively normal subjects to determine the association between anemia at follow-up and MCI.

The team found that MCI occurred more often in anemic than non-anemic subjects. The unadjusted odds ratio (OR) was 2.59 (P<0.001). The OR after adjustment for age, gender, and years of education was 2.15 (P=0.002).

In a third analysis, the researchers adjusted for the aforementioned variables as well as body mass index, high-sensitivity C-reactive protein, glomerular filtration rate, cholesterol, serum iron, hypertension, diabetes mellitus, history of coronary heart disease, history of stroke, history of cancer, APOE4, smoking, severe depressive symptoms, and use of antidepressants. The OR after adjustment for these factors was 1.92 (P=0.04).

Similar results were found for aMCI and naMCI. The researchers said this suggests that having a low hemoglobin level may contribute to cognitive impairment via different pathways.

The team believes that, overall, their study results indicate that anemia is associated with an increased risk of MCI independent of traditional cardiovascular risk factors. They said the association between anemia and MCI has important clinical relevance because—depending on etiology—anemia can be treated effectively, and this might provide means to prevent or delay cognitive decline.

Anemia tied to cognitive impairment