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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.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- BLSA=
- Baltimore Longitudinal Study of Aging;
- BMI=
- body mass index;
- CI=
- confidence interval;
- CR=
- creatinine;
- DSM-III-R=
- Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised;
- HR=
- hazard ratio;
- LDL=
- low-density lipoprotein;
- UFC=
- urinary free cortisol
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received May 31, 2016.
- Accepted in final form October 17, 2016.
- © 2016 American Academy of Neurology
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