PT  - JOURNAL ARTICLE
AU  - Wolters, Frank J.
AU  - Zonneveld, Hazel I.
AU  - Licher, Silvan
AU  - Cremers, Lotte G.M.
AU  - , 
AU  - Ikram, M. Kamran
AU  - Koudstaal, Peter J.
AU  - Vernooij, Meike W.
AU  - Ikram, M. Arfan
TI  - Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI
AID  - 10.1212/WNL.0000000000008003
DP  - 2019 Aug 27
TA  - Neurology
PG  - e917--e926
VI  - 93
IP  - 9
4099  - http://n.neurology.org/content/93/9/e917.short
4100  - http://n.neurology.org/content/93/9/e917.full
SO  - Neurology2019 Aug 27; 93
AB  - Objective To determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population.Methods Serum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion.Results During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09–1.52]; highest vs middle quintile 1.20 [1.00–1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%–62%) and 41% (15%–74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001).Conclusion Low and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.AD=Alzheimer disease; CI=confidence interval; DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised; FA=fractional anisotropy; GMS=Geriatric Mental Schedule; HDL=high-density lipoprotein; HR=hazard ratio; MD=mean diffusivity; MMSE=Mini-Mental State Examination; WMH=white matter hyperintensity