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Neurology. 2011 Jul 19;77(3):219-26. doi: 10.1212/WNL.0b013e318225aaa9. Epub 2011 Jul 13.

Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis.

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  • 1Rush Alzheimer's Disease Center, Rush University Medical Center, Armour Academic Facility, Suite 1038, 600 South Paulina St., Chicago, IL 60612, USA. Raj_C_Shah@rush.edu



To test the hypothesis that level of hemoglobin is associated with incident Alzheimer disease (AD).


A total of 881 community-dwelling older persons participating in the Rush Memory and Aging Project without dementia and a measure of hemoglobin level underwent annual cognitive assessments and clinical evaluations for AD.


During an average of 3.3 years of follow-up, 113 persons developed AD. In a Cox proportional hazards model adjusted for age, sex, and education, there was a nonlinear relationship between baseline level of hemoglobin such that higher and lower levels of hemoglobin were associated with AD risk (hazard ratio [HR] for the quadratic of hemoglobin 1.06, 95% confidence interval [CI] 1.01-1.11). Findings were unchanged after controlling for multiple covariates. When compared to participants with clinically normal hemoglobin (n = 717), participants with anemia (n = 154) had a 60% increased hazard for developing AD (95% CI 1.02-2.52), as did participants with clinically high hemoglobin (n = 10, HR 3.39, 95% CI 1.25-9.20). Linear mixed-effects models showed that lower and higher hemoglobin levels were associated with a greater rate of global cognitive decline (parameter estimate for quadratic of hemoglobin = -0.008, SE -0.002, p < 0.001). Compared to participants with clinically normal hemoglobin, participants with anemia had a -0.061 z score unit annual decline in global cognitive function (SE 0.012, p < 0.001), as did participants with clinically high hemoglobin (-0.090 unit/year, SE 0.038, p = 0.018).


In older persons without dementia, both lower and higher hemoglobin levels are associated with an increased hazard for developing AD and more rapid cognitive decline.

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