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

Abstract

AbstractBackgroundChronic stress has been studied as a potential lifestyle risk factor for Alzheimer's disease (AD). Prolonged stress can lead to alterations in diurnal patterns of cortisol. This study aims to investigate the relationship between diurnal cortisol patterns, cognition, and AD biomarkers in memory clinic patients.MethodParticipants diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or AD dementia were recruited from Karolinska University Hospital memory clinic in Sweden (n=155). Baseline cognition was measured using five cognitive domains (memory, working memory, processing speed, perceptual reasoning, overall cognition), operationalized as average z‐scores. Diurnal cortisol patterns were assessed using five salivary cortisol measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime cortisol levels (AM/PM ratio), and total daily output. AD biomarkers Aβ42, total tau (T‐Tau), and phosphorylated tau (P‐Tau) were measured from cerebrospinal fluid. Cognition was measured at follow‐up (average 32 months) in a subsample of participants (n=57).ResultAwakening cortisol levels were significantly higher in AD dementia compared with SCI. Greater cortisol awakening response was associated with better memory performance (OR= 1.57, 95% CI: [1.10 – 2.23]), while a greater AM/PM ratio (OR= 2.21, 95% CI: [1.15 – 4.25]) and lower bedtime cortisol levels (OR= .64, 95% CI: [.40 – 1.01]) were associated with better overall cognition. Cortisol measures were not associated with cognitive decline during follow‐up or with AD biomarkers in the full sample. However, in stratified analyses, higher awakening cortisol levels were associated with lower CSF Aβ42 in amyloid‐positive participants (b= ‐60.13; 95% CI [‐102.73 ‐ ‐17.52]), while higher bedtime cortisol levels (b= .09; 95% CI [.02 ‐ .17]) and a lower AM/PM ratio (b= ‐.12; 95% CI [‐.23 ‐ ‐.02]) were associated with higher CSF T‐Tau in amyloid‐negative participants.ConclusionThis study shows that diurnal cortisol patterns are associated with cognitive performance in memory clinic patients. In people without amyloid pathology, cortisol may affect cognition through neurodegeneration‐related mechanisms, leading to the observed correlation with T‐Tau. Meanwhile, in amyloid‐positive participants, the greater pathology level may affect cortisol patterns. Further research should investigate the complex relationship between cortisol, cognition, and brain pathology.