Post-awakening cortisol and resilience: unravelling their impact on cognitive decline

Age-associated cognitive decline is a growing social problem and a major concern for older adults, highlighting the need to identify modifiable factors to mitigate it. The basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis, and, especially, the post-awakening cortisol levels, seems to play a key role in cognitive performance related to functions dependent on the prefrontal cortex and hippocampus. Regulating these cortisol levels is crucial in this context, and resilience has been recognized as vital for successful aging and cognitive functioning. This study was designed to examine how post-awakening cortisol levels (both the cortisol awakening response, CAR (AUCi) and total post-awakening cortisol secretion, AUCg) could predict cognitive decline across different domains, and explore the role of resilience in this relationship. To investigate this, a follow-up study conducted between 2018 (Wave 1, W1) and 2022 (Wave 2, W2) included 53 healthy adults who completed tasks assessing verbal fluency, executive function, declarative memory, and resilience in both waves to study the cognitive decline. Moreover, in W1, participants provided four morning saliva samples on two consecutive working days to assess post-awakening cortisol levels on days that were different from the cognitive testing sessions. Results showed a negative association between AUCg and both phonemic and semantic fluency decline, but not in other cognitive domains, indicating a beneficial effect of post-awakening cortisol secretion on cognitive maintenance that appears be domain specific. In addition, resilience positively mediated the association between the CAR and the maintenance of semantic fluency. These findings underscore the role of post-awakening cortisol levels in supporting resilience and protecting prefrontal cortex-dependent functions, such as semantic fluency, over functions reliant on the hippocampus.