The relationship between cortisol and cognitive function in healthy older people: The moderating role of Apolipoprotein E polymorphism

Abstract

The Apolipoprotein E4 (ApoE-ε4) allele has been suggested as the main risk factor for late onset Alzheimer's disease (AD), whereas the ApoE-ε2 allele has been proposed as a protective factor. These proposals have increased the interest in the effect of the ApoE genotype in healthy people. Additionally, high cortisol levels have been related to negative effects on cognition. However, few studies have investigated the relationship between cognitive performance and cortisol, taking into account the different ApoE alleles. For this reason, the aim of this study was to evaluate different cognitive domains (declarative and working memory, attention, and executive function) and their relationship with cortisol, considering the ApoE-ε2, ApoE-ε3, and ApoE-ε4 alleles in healthy older people (55-77 years old). Two saliva samples were collected during the neuropsychological session to obtain cortisol levels and the ApoE genotype. Results showed an association between the ApoE genotype and declarative memory, specifically learning ability, where ApoE-ε2 group performed better than ApoE-ε4 and ApoE-ε3 groups. No differences in cortisol levels were obtained considering the ApoE genotype. In addition, higher mean cortisol levels were related to a worse performance on declarative memory, for the whole sample, and when considering the three allelic variation, for the ApoE-ε4 group. On the contrary, an increase of cortisol levels during the neuropsychological session was associated to a better performance on declarative memory for the whole sample, and for the ApoE-ε3 group when considering the three alleles. Besides, ApoE-ε3 group also showed an association between higher mean cortisol levels and a better attention performance. Therefore, our results suggest that carrying the ApoE-ε4 allele may be a vulnerability factor in the adverse effects of Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation on cognition during aging, while ApoE-ε3 allele could be associated to a more adaptive HPA axis response.

Acute Cortisol Levels and Memory Performance in Older People with High and Normal Body Mass Index

“…The evidence for this age-related decrease in sensitivity comes from studies investigating the effects of stress-induced and/or pharmacologically-induced acute increases in cortisol levels on memory performance (Hidalgo et al, 2015; Porter, Barnett, Idey, Mcguckin, & O’brien, 2002; Yehuda, Harvey, Buchsbaum, Tischler, & Schmeidler, 2007; Pulopulos et al, 2013; Pulopulos et al, 2015; Wolf et al, 2001). Moreover, two recent studies indicate that the relationship between cortisol levels under non-stressful conditions and memory performance in older people would only be observed in individuals who are carriers of the ApoE–ε4 allele, which is considered a high-risk factor for developing Alzheimer Disease (Lee et al, 2008; Montoliu et al, 2018). Given the BMI-related increase in MR, it is critical to understand whether differences in BMI contribute to a different relationship between cortisol and memory performance in older people.…”

Monobutyrin and monovalerin improve gut–blood–brain biomarkers and alter gut microbiota composition in high-fat fed apolipoprotein-E-knockout rats

“…This effect was associated with increased serum SCFAs measured within 5 h upon waking 15 . In healthy or non-demented elderly, a relationship between higher salivary cortisol levels and worse memory performance has been reported, especially in those carrying the main risk factor of late onset of AD allele ApoE4, suggesting that they are more vulnerable to cognition decline during aging 38 , 39 . Corticosterone level is also associated with the gut microbiota due to a bidirectional interaction between the hypothalamic–pituitary–adrenal (HPA) axis and gut microbiota.…”

Understanding the Physiological Links Between Physical Frailty and Cognitive Decline

“…When the aMCI group was stratified by the APOEε4 status, significant differences were found in the levels of IL-6 and IFN-γ between the lowand high-risk groups and the control group [162], suggesting that some genetic factors are important. The loss of the APOEε4 allele may be a vulnerability factor that contributes to the adverse effects of HPA axis dysregulation on cognition and has been suggested as the main risk factor for late-onset AD, while the APOEε3 allele was associated with a more adaptive HPA axis response [163].…”