title: Long-term cortisol measures predict Alzheimer disease risk.
abstract: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Gilda E
authors.initials: GE
authors.lastname: Ennis
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: 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.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.affiliation: 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.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: 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.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Brien
authors.affiliation: 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.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Moffat
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000652:urine*; D015142:Baltimore; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003404:Creatinine; D006854:Hydrocortisone