A study that followed more than 12,000 people for over 12 years adds significant weight to the idea that hemoglobin level is an important risk factor for Alzheimer’s and other dementias. Scientists led by M. Arfan Ikram at Erasmus Medical Center, Rotterdam, the Netherlands, found that both high and low levels of serum hemoglobin associate with increased risk. In their Neurology paper published July 31, they report that cardiovascular disease could mediate the association.
- People with high or low serum hemoglobin are at greater risk for dementia.
- They also have cerebrovascular disease and reduced brain connectivity.
- The mechanism underlying these associations is unclear.
“This analysis replicates prior work highlighting the relationship between low and high levels of hemoglobin and an increased risk of dementia and Alzheimer’s disease,” wrote Raj Shah, Rush University, Chicago, to Alzforum (Jul 2011 news on Shah et al., 2011). “The inclusion of magnetic resonance imaging provides insight into the mechanisms of how hemoglobin levels may be impacting brain structure.”
First author Frank Wolters and colleagues used longitudinal data from the ongoing population-based Rotterdam Study. Serum hemoglobin was measured at baseline in 12,305 participants without dementia. A total of 5,267 had also had an MRI at some point during the study. Participants were followed for an average of 12.1 years.
At the time of analysis, 1,520 individuals had been diagnosed with dementia, of whom 1,194 had AD. Those in the lowest and highest quintiles for hemoglobin levels were more likely to develop dementia than those in the middle quintile, with hazard ratios of 1.29 and 1.20 for low and high Hbg, respectively. People who were clinically diagnosed with anemia, that is, having less than 8.1 mmol/L Hbg for men and less than 7.5 mmol/L for women, had a 1.34-fold risk of all-cause dementia and a 1.41-fold increase in the risk for AD. Associations with MRI markers followed the same trend, with both high and low hemoglobin correlating with more white-matter hyperintensities and weaker structural connectivity, as measured by diffusivity analysis. People with anemia had more cerebral microbleeds.
Exactly how shifts in hemoglobin levels increase risk for dementias remains to be seen. It could be related to low oxygenation at the low end, and greater risk of blood-clot-related ischemia at the other. More work will be needed to understand if hemoglobin levels can be modified to maintain brain health in older adults, Shah wrote. Further study will determine if these findings hold up in non-European ethnicities and geographic regions, the authors noted.—Gwyneth Dickey Zakaib
- Shah RC, Buchman AS, Wilson RS, Leurgans SE, Bennett DA. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011 Jul 19;77(3):219-26. PubMed.
- Koyama A, Hashimoto M, Tanaka H, Fujise N, Matsushita M, Miyagawa Y, Hatada Y, Fukuhara R, Hasegawa N, Todani S, Matsukuma K, Kawano M, Ikeda M. Malnutrition in Alzheimer's Disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration: Comparison Using Serum Albumin, Total Protein, and Hemoglobin Level. PLoS One. 2016;11(6):e0157053. Epub 2016 Jun 23 PubMed.
- Faux NG, Rembach A, Wiley J, Ellis KA, Ames D, Fowler CJ, Martins RN, Pertile KK, Rumble RL, Trounson B, Masters CL, AIBL Research Group, Bush AI. An anemia of Alzheimer's disease. Mol Psychiatry. 2014 Nov;19(11):1227-34. Epub 2014 Jan 14 PubMed.
- Wolters FJ, Zonneveld HI, Licher S, Cremers LG, Heart Brain Connection Collaborative Research Group,, Ikram MK, Koudstaal PJ, Vernooij MW, Ikram MA. Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI. Neurology. 2019 Jul 31; PubMed.