Stress and Alzheimer’s disease: Linking salivary cortisol to biomarkers of neurodegeneration and cognitive decline in a memory clinic cohort

Abstract

AbstractBackgroundPsychosocial stress has been shown to affect cognitive performance negatively and to increase the risk of developing dementia. Cortisol, a hormone thought to mediate several of the effects of chronic stress, has been shown to be elevated in Alzheimer’s disease (AD) patients. Interestingly, cortisol induces inflammatory responses that are detrimental to brain function. However, the relationship of this hormone with AD pathology, neuroinflammation, synaptic degeneration and neuronal survival is not well understood. The aim of this study is to investigate the interconnection of cortisol with CSF biomarkers of AD pathology, inflammation and synaptic dysfunction and with the serum neurotrophic factor BDNF and its precursor, proBDNF.MethodCross‐sectional analyses were performed on data from a total of 158 memory clinic patients with subjective cognitive decline (SCI, n=55), mild cognitive impairment (MCI, n=62) and Alzheimer’s disease (AD, n=41), from the Karolinska University Hospital in Sweden. Six timepoint diurnal salivary cortisol measurements, serum BDNF (both mBDNF and proBDNF) and the following CSF analytes were quantified: a neuroinflammation marker (chitinase‐3‐like protein 1 (YKL‐40)), markers of synaptic degeneration (synaptotagmin‐1, neurogranin and SNAP‐25) and AD pathology markers (Aβ1‐42, t‐tau and p‐tau). Linear regression models were performed for all participants and for each diagnostic subgroup, to examine the relationship between cortisol and the biomarkers, adjusting for age, sex, education and diagnosis. ANOVA, or Kruskal‐Wallis tests were applied to compare marker levels between the diagnostic groups.ResultPositive associations were observed between salivary cortisol and CSF t‐tau, neurogranin and SNAP‐25. Salivary cortisol was also associated with lower peripheral proBDNF levels in the AD group. Increased awakening cortisol was associated with lower proBDNF levels in all participants, while a similar association could be observed for bedtime cortisol in the AD group only. There was no relationship between cortisol and YKL‐40, however YKL‐40 was associated with the synaptic markers. SNAP‐25 and neurogranin were higher in AD compared to SCI and MCI participants, confirming results from previous reports.ConclusionOur findings support an association of cortisol hypersecretion with neurodegeneration, synaptic dysfunction and the reduction of proBDNF in the periphery, which needs further investigation.