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Both Extremes of Hemoglobin Linked to Dementia Risk

July 31, 2019

By Will Boggs MD

NEW YORK—Both low and high hemoglobin levels are associated with an increased risk of dementia, according to findings from the population-based Rotterdam Study.

"Abnormal levels of hemoglobin, in particular anemia, are common in the population and need to be taken seriously," Dr. Frank J. Wolters from Erasmus Medical Center, Rotterdam, The Netherlands told Reuters Health by email. "In anticipation of further studies that clarify the underlying mechanisms and the effects of treating anemia on brain health or cognition, results from this study could add to well-acknowledged indications just another incentive to prompt diagnosis and treatment of any underlying cause of anemia."

Low hemoglobin levels have been associated with a number of adverse health outcomes, but there is limited evidence about the association between the range of hemoglobin levels and the risk of dementia.

Dr. Wolters and colleagues used data from 12,305 participants in the Rotterdam Study to examine the association between hemoglobin levels or anemia and risk of dementia. In a subset of 5319 participants who underwent MRI, they also studied imaging markers of vascular brain disease, structural connectivity, and cerebral perfusion

Overall, 6.1% of participants had anemia, and 1520 individuals developed dementia during a mean follow-up of 12.1 years.

Compared with the middle quintile of hemoglobin levels (8.57-8.99 mmol/L or 13.80-14.40 g/dL), the lowest quintile (<8.11 mmol/L or <13.07 g/dL) was associated with a 29% increased risk of all-cause dementia and a 36% increased risk of Alzheimer disease, the researchers reported July 31st online in Neurology.

The highest quintile of hemoglobin levels (>9.40 mmol/L or >15.17 g/dL) was associated with a 20% increased risk of all-cause dementia, compared with the middle quintile.

Anemia (hemoglobin <8.06 mmol/L or <13.0 g/dL for men and <7.45 mmol/L or <12.0 g/dL for women) was associated with a 34% increased risk of all-cause dementia and a 41% increased risk of Alzheimer disease.

The volume of white matter hyperintensities (WMH) and structural connectivity were also worse in both the lower and upper ranges of hemoglobin levels, and structural connectivity was significantly worse in individuals with anemia than in those without anemia.

Low levels of hemoglobin (but not high levels) were associated with higher prevalence of microbleeds, whereas neither hemoglobin levels nor anemia was related to the presence of lacunar or cortical infarcts.

Hemoglobin levels were linearly associated with cerebral perfusion, with each 1 mmol/L increase in hemoglobin conferring a 3.2 mL/100 mL/minute lower cerebral perfusion.

"Anemia is often underdiagnosed and undertreated, which may have serious implications for brain health," Dr. Wolters said. "However, before we can use these findings to recommend interventions, it is important that additional studies are done to establish whether hemoglobin is in fact the culprit, or that concomitant vascular or metabolic changes are the culprit in increasing dementia risk."

Dr. Laura Winchester from Warneford Hospital, Oxford, UK, who recently found lower hemoglobin levels to be associated with poor cognitive function and Alzheimer disease, told Reuters Health in an email interview, "There is a known association between dementia risk and anemia (low hemoglobin). The interesting result here is to confirm in the same sample set that there is also a risk associated with high hemoglobin. By qualifying this result with brain MRI data, the authors have provided further weight to this evidence and present a thorough study of the relationship between hemoglobin and dementia."

"Identifying modifiable risk factors for dementia has become increasingly important as an approach to reduce disease incidence," she said. "By showing that changes in hemoglobin levels are related to dementia, the authors present anemia as a risk factor which, if proven to be causal, could be used as a target to reduce the likelihood of developing dementia."


Neurology 2019.

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