Gilda E Ennis1, Yang An1, Susan M Resnick1, Luigi Ferrucci1, Richard J O'Brien1, Scott D Moffat2. 1. From the School of Psychology (G.E.E., S.D.M.), Georgia Institute of Technology, Atlanta; Laboratory of Behavioral Neuroscience (Y.A., S.M.R.) and Longitudinal Studies Section (L.F.), National Institute on Aging, Baltimore, MD; and School of Medicine (R.J.O.), Johns Hopkins University, Baltimore, MD. Dr. O'Brien is now at the School of Medicine, Duke University, Durham, NC. 2. From the School of Psychology (G.E.E., S.D.M.), Georgia Institute of Technology, Atlanta; Laboratory of Behavioral Neuroscience (Y.A., S.M.R.) and Longitudinal Studies Section (L.F.), National Institute on Aging, Baltimore, MD; and School of Medicine (R.J.O.), Johns Hopkins University, Baltimore, MD. Dr. O'Brien is now at the School of Medicine, Duke University, Durham, NC. scott.moffat@psych.gatech.edu.
Abstract
OBJECTIVE: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. METHOD: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. RESULTS: UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. CONCLUSIONS: Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD.
OBJECTIVE: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. METHOD: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. RESULTS: UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. CONCLUSIONS: Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD.
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