title: Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis.
abstract: OBJECTIVE
  To test the hypothesis that level of hemoglobin is associated with incident Alzheimer disease (AD).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rush 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
authors.forename: R C
authors.initials: RC
authors.lastname: Shah
authors.forename: A S
authors.initials: AS
authors.lastname: Buchman
authors.forename: R S
authors.initials: RS
authors.lastname: Wilson
authors.forename: S E
authors.initials: SE
authors.lastname: Leurgans
authors.forename: D A
authors.initials: DA
authors.lastname: Bennett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000453:epidemiology*; D000740:Anemia / Q000453:epidemiology; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000209:etiology; D009483:Neuropsychological Tests; D018962:Phlebotomy / Q000379:methods; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D012111:Residence Characteristics; D012189:Retrospective Studies
chemical_list: D006454:Hemoglobins