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.

Figure 1. Hazard ratio for incident Alzheimer disease (AD) as a function of baseline hemoglobin level

(A) The curve is generated from a proportional hazards model with age, sex, education, and linear and quadratic terms for hemoglobin. Reference hazard ratio was for the hemoglobin level associated with the lowest hazard ratio (13.7 g/dL). (B) The distribution of hemoglobin for the cohort depicts data available for interpreting the relationship of baseline level to risk of AD.

Figure 2. Rate of annual cognitive decline as a function of baseline hemoglobin level

(A) The curve is generated from a mixed-effects model with time, age, sex, education, linear and quadratic terms for hemoglobin, and each term's interaction with time. Y-axis shows the annual rate of change in cognition with a more negative value associated with a more rapid rate of decline. Lowest annual rate of cognitive decline was associated with hemoglobin of 13.7 g/dL. (B) The distribution of hemoglobin for the cohort depicts data available for interpreting the relationship of baseline level to annual rate of cognitive decline.