Cortisol, cognition and Alzheimer's disease biomarkers among memory clinic patients

Abstract

Objective: This study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer's disease (AD) biomarkers in memory clinic patients.

Method: Memory clinic patients were recruited from Karolinska University Hospital in Sweden (n=155). Diurnal cortisol patterns were assessed using five measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime levels (AM/PM ratio) and total daily output. Cognition was measured in five domains: memory, working memory, processing speed, perceptual reasoning and overall cognition. AD biomarkers Aβ₄₂, total tau and phosphorylated tau were assessed from cerebrospinal fluid (CSF). Cognition was measured at follow-up (average 32 months) in a subsample of participants (n=57).

Results: In assessing the associations between cortisol and cognition, higher awakening cortisol levels were associated with greater processing speed at baseline. No relationship was found between diurnal cortisol patterns and change in cognition over time or CSF AD biomarkers in the total sample. After stratification by CSF Aβ₄₂ levels, higher awakening cortisol levels were associated with worse memory performance in amyloid-positive participants. In amyloid-negative participants, higher bedtime cortisol levels and a lower AM/PM ratio were associated with lower overall cognition, greater awakening cortisol levels were associated with better processing speed, and a higher AM/PM ratio was associated with better perceptual reasoning. Additionally, higher awakening cortisol levels were associated with lower CSF Aβ₄₂ levels in amyloid-positive participants, while higher bedtime cortisol levels and a lower AM/PM ratio were associated with higher CSF total tau in amyloid-negative participants.

Conclusions: Our findings suggest that diurnal cortisol patterns are associated with cognitive function and provide new insights into the association between diurnal cortisol patterns and AD-related CSF biomarkers. Further research is needed to examine the complex relationship between cortisol, cognition and brain pathology.

Keywords: ALZHEIMER'S DISEASE; AMYLOID; COGNITION; STRESS.

Figure 1

Diurnal patterns of cortisol levels, by (A) diagnostic category and by (B) amyloid pathology status. AD, Alzheimer’s disease; Aβ, beta-amyloid; Aβ–, CSF Aβ42 level above 550 ng/L, Aβ+, CSF Aβ42 level below 550 ng/L; CSF, cerebrospinal fluid; MCI, mild cognitive impairment; SCI, subjective cognitive impairment.