ANEMIA AND DEMENTIA RISK

Among older adults, anemia is associated with an increased risk of developing dementia, a new study shows.

"We found that if there was anemia at baseline, the risk of dementia was increased by about 60%. This was slightly reduced after adjusting for other factors. But there was still a 40-50% increase in risk which was still quite significant. Anemia is of course a marker of general frailty, which will also correlate with dementia but we tried to control for this," senior author, Kristine Yaffe, MD, University of California San Francisco, toldMedscape Medical News.

She acknowledged that this is not enough evidence to say that correcting anemia will reduce the risk for dementia.

"We need another study where the anemia is treated to make this claim, but we could say that this is another reason to check for anemia more often in older people and to treat it."

"I am not suggesting that these results should prompt people to rush out and start taking large doses of iron. If they want to rush out and do anything they should make sure they have an annual check up and get their hemoglobin measured, and if it is low get it corrected, under medical supervision," Dr. Yaffe added.

The study is published online July 31 in Neurology.

Mechanism

A few other studies have suggested a link between anemia and dementia.

"But while these have been tantalizing they were far from definitive because they were cross-sectional in design — they just found an association at one point in time.

"It is very difficult to attribute a causal relationship under these circumstances. People with dementia generally do not eat well, take their medication properly, or look after themselves very well, so anemia is likely to be more common," said Dr. Yaffe.

In the current study, the researchers tried to control for some of these issues by doing a prospective study in patients who started off without dementia and controlling for comorbid conditions.

'We also had a similar mix of men and women and blacks and whites. So our study adds weight to previous evidence. In fact I would say it was by far the most rigorous study to address this question to date," said Dr. Yaffe.

For the study, 2552 older adults (mean age, 76.1 years; 38.9% black; 51.8% female) participating in the Health, Aging, and Body Composition study who were free of dementia at baseline underwent a blood test for anemia and were then followed for 11 years.

Anemia was defined using World Health Organization criteria (hemoglobin concentration of 13 g/dL for men and 12 g/dL for women). Cognitive function was assessed at years 1, 3, 5, 8, 10, and 11 with the Modified Mini-Mental State test. Dementia diagnosis was determined by dementia medication use, hospital records, or a decline in the Mini-Mental State score of more than 1.5 standard deviation from the mean.

Results showed that 15.4% of the population had anemia at baseline, and 17.8% of the participants developed dementia during follow-up.

In the unadjusted model, those with baseline anemia had a 64% increased risk for dementia.

Table. Effect of Anemia on Risk for Dementia

Variable	Anemia (%)	No Anemia (%)	Hazard Ratio (95% Confidence Interval)
Dementia developed during follow up	23	17	1.64 (1.30 - 2.07)

The association remained significant after adjustment for demographics, APOE ε4, baseline Mini-Mental State score, comorbid conditions, and renal function. Additional adjustment for other anemia measures (mean corpuscular volume, red cell distribution width), erythropoietin, and C-reactive protein did not appreciably change the results. There was no interaction by sex and race on risk of developing dementia.

The researchers suggest several possible mechanisms that may explain the link, but Dr. Yaffe said she thought the most likely mechanism would be low levels of hemoglobin leading to low levels of circulating oxygen, which could have an effect on the brain over many years.

Asked how these results square with other research which has suggested Alzheimer's disease may be linked with high levels of iron, Yaffe said she was not that familiar with that research, but she suggested that it was probably best that iron levels were not too high or too low.

The study was supported in part by the Intramural Research Program of the National Institutes of Health and National Institute on Aging. Dr. Yaffe reports she has served on data safety monitoring boards for Takeda and the National Institutes of Health and has served as a consultant for Novartis.

Neurology. Published online July 31, 2013. 2013;81:528-533. Abstract