Long-term cortisol measures predict Alzheimer disease risk.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ennis, GE; An, Y; Resnick, SM; Ferrucci, L; O'Brien, RJ; Moffat, SD

Published Date

  • January 24, 2017

Published In

Volume / Issue

  • 88 / 4

Start / End Page

  • 371 - 378

PubMed ID

  • 27986873

Pubmed Central ID

  • 27986873

Electronic International Standard Serial Number (EISSN)

  • 1526-632X

Digital Object Identifier (DOI)

  • 10.1212/WNL.0000000000003537


  • eng

Conference Location

  • United States