Long-term cortisol measures predict Alzheimer disease risk

Area of Science:

• Endocrinology
• Neuroscience
• Gerontology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
• Cortisol, a key stress hormone, plays a role in various physiological processes.
• Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, involving cortisol, has been implicated in aging and disease.

Purpose of the Study:

• To investigate if long-term cortisol measures predict the risk of developing Alzheimer's disease.
• To explore the relationship between cortisol dysregulation and AD risk using longitudinal data.

Main Methods:

• Prospective longitudinal study using data from the Baltimore Longitudinal Study of Aging (BLSA).
• Analysis of multiple 24-hour urinary free cortisol (UFC) and creatinine (Cr) samples over an average of 10.56 years.
• Calculation of UFC/Cr ratio and assessment of within-person mean, slope, and coefficient of variation to measure cortisol regulation; Cox regression used to predict AD risk.

Main Results:

• Elevated UFC/Cr level and UFC/Cr variability significantly predicted AD risk up to 2.9 years before diagnosis.
• Higher UFC/Cr level and variability were associated with a 1.31-fold and 1.38-fold increase in AD risk, respectively.
• Sensitivity analysis indicated these predictors were significant even 6 years before AD onset.

Conclusions:

• Cortisol dysregulation, characterized by high UFC/Cr level and variability, may influence AD pathology expression.
• These cortisol measures could serve as preclinical biomarkers for Alzheimer's disease.
• Longitudinal assessment of cortisol offers insights into AD pathogenesis and risk prediction.