the discovery of cortisol receptors in the brain (McEwen, Weiss, & Schwartz, 1968
), researchers have been interested in understanding how cortisol is associated with cognitive function (CF). Although much of the research examining links between cortisol and CF has relied on the experimental manipulation of cortisol levels (Lupien & McEwen, 1997
; Lupien et al., 2005
), considerable efforts have been devoted to examining links between naturally occurring cortisol levels and CF (e.g., Seeman, McEwen, Singer, Albert, & Rowe, 1997
). The diurnal rhythm of cortisol is garnering considerable empirical attention for its utility as an indicator of not only stress but also general neuroendocrine function and its potential links to physical, emotional, and cognitive health (Adam & Kumari, 2009
). The current study was conducted to examine associations between CF and the dynamics of daily cortisol across the adult life span in a national sample of adults.
Cortisol is a hormone secreted by the hypothalamic–pituitary–adrenal (HPA) axis. It is released in response to stress (Dickerson & Kemeny, 2004
) but is more than just a product of the stress response and is a widely used indicator of general neuroendocrine/HPA axis health (Hellhammer et al., 2007
; Miller, Chen, & Zhou, 2007
). Cortisol exhibits a diurnal pattern, reaching its peak within an hour after waking and declining thereafter, until reaching a nadir at approximately midnight (Kirschbaum & Hellhammer, 1989
; Pruessner et al., 1997
). The initial rise referred to as the morning rise (MR) and the decline thereafter as the diurnal cortisol slope (DCS; Adam & Kumari, 2009
; Cohen et al., 2006
). Robust MR and DCS slopes are thought to reflect a healthy HPA axis function and flattened profiles being unhealthy (Adam & Kumari, 2009
; Stone et al., 2001
Additional evidence for patterns of healthy HPA axis function comes from a recent meta-analysis by Miller and colleagues (2007)
considering associations between chronic stress and HPA axis dysregulation. The authors found that chronic stress-related HPA dysregulation manifests as a flatter MR and DCS and higher overall total cortisol output. Such dysregulation is also evidenced in lower morning cortisol levels and higher afternoon/evening levels. These convergent patterns suggest that there are certain characteristics of diurnal cortisol indicative of healthy HPA axis function (i.e., steeper MR and DCS, higher morning levels, and lower afternoon/evening levels), which can inform hypotheses associations between cortisol and other constructs of theoretical interest.
CF is one construct that has been linked to cortisol and received considerable empirical attention. Cortisol is thought to have proximal effects on CF by interfering with neural transmission and subsequent behavioral performance (Lupien & Lapage, 2001
; Wolf, 2003
; however, see Roozendaal, 2002
) and more durable and distal effects via neuronal death from prolonged exposure to cortisol (Sapolsky, 1992
). Preferential densities of cortisol receptors in the hippocampus and frontal lobes have led researchers examining cognition–cortisol links to focus on tasks measuring episodic memory (EM), which is governed by the hippocampus (Squire, 1992
), and executive function (EF), which is governed by the frontal lobes (Stuss & Knight, 2002
). Although the majority of research linking cortisol to CF has used experimentation to examine how acute changes in cortisol are associated with CF (see Lupien & Lapage, 2001
; Lupien & McEwen, 1997
for reviews), there is a growing body of work examining how naturally occurring cortisol levels and rhythms are associated with CF.
Flatter DCS slopes have been associated with poorer EM among older adults experiencing memory deficits and depressive symptoms (Fiocco, Wan, Weekes, Pim, & Lupien, 2006
), older adults positive for the APOE-ϵ4 allele, a known risk factor for dementia (Gerritsen, Comijs, Deeg, Penninx, & Geerlings, in press
), and poorer EF among community-dwelling older adults (Beluche, Carrière, Ritchie, & Ancelin, 2009
). For morning cortisol levels, Lupien and colleagues have shown that annual increases in 24-hr average basal cortisol levels are associated with poorer EM (Lupien et al., 1994
) and smaller hippocampal volume (Lupien et al., 1998
) among older adults. Similarly, Kuningas and colleagues (2007)
found that higher morning cortisol levels were associated with poorer global CF, attention, and processing speed in older adults aged 85 years and older, whereas Beluche and colleagues (2009)
found that higher morning cortisol levels were associated with poorer EF and EM in a community-dwelling sample of older adults. In contrast, Gerritsen and colleagues (in press)
found that higher waking cortisol levels were associated with poorer EM performance but only among older adults carrying the APOE-ϵ4, whereas Kalmijn and colleagues (1998)
found no reliable association between morning cortisol levels and an index of global CF. Finally, regarding afternoon/evening cortisol levels, Carlson and Sherwin (1999)
observed that older adults with higher afternoon levels of cortisol exhibited poorer EM performance, whereas 12-hr overnight basal cortisol levels of Seeman and colleagues (1997)
were associated with poorer EM at baseline and greater declines in EM over a 2.5-year period among women. Similarly, Gerritsen and colleagues (in press)
found that higher cortisol levels in the evening, just before bed, were associated with poorer EM performance among older adults possessing the APOE-ϵ4 allele.
Research examining associations between the DCS, afternoon/evening cortisol levels, and CF seems to be rather consistent showing that a flatter DCS and higher levels of afternoon evening cortisol are associated with poorer CF. Findings regarding morning cortisol are mixed, possibly due to the timing of the cortisol assessments. Basal levels reported by Lupien were the average of samples taken over a 24-hr period reflecting average cortisol output over a given time period that includes morning levels. Second, Kuningas and Beluche observed that higher levels of cortisol were associated with poorer CF, but Kuningas’ morning sample was taken before 11 a.m. and Beluche's was taken at least 1 hr after waking. Thus, in both studies, the samples were possibly taken after the cortisol levels were likely already starting to decline. Positive associations between CF and morning cortisol levels might be expected proximal to waking when cortisol levels are expected to be higher and increasing, whereas negative associations might be expected once levels have started to decline.
Previous research on cortisol and CF has also largely focused on levels and dynamics of cortisol being important for predicting decrements in CF, implying a particular direction of effect. More recently, researchers have considered that cortsiol and CF may have a more dynamic relationship. Existing models of HPA axis function support this notion. Although cortisol is released from the adrenals and binds to receptors in the hippocampus and frontal lobes, both these brain regions also provide feedback to the hypothalamus as part of HPA axis downregulation (Lupien & Lapage, 2001
). Empirical support for such bidirectional associations also exists. Lupien and colleagues (2005)
showed that evidence of childrens’ CF, with respect to making emotional attributions, significantly predicted morning basal cortisol levels. Using prospective longitudinal data, Power, Li, and Hertzman (2008)
showed that lower childhood CF was predictive of a flatter DCS forty-five years later during adulthood. Furthermore, Applehans and Luecken (2006)
found that EF was associated with diminished cortisol reactivity to threat cues.
Recent theoretical development regarding CF as an important predictor of health complements these empirical findings. Williams, Suchy, and Rau (2009)
have reviewed evidence linking individual differences in CF, particularly EF, to better self-regulation, suggesting that EF is a potentially important characteristic for understanding differential exposure, reactivity, and recovery from stress. Similarly, Gottfredson and Deary (2004)
have suggested that CF, particularly intellectual abilities related to EF, may be associated with better health and longevity because of increased skills useful in adaptation and preventing chronic disease. Here, CF may be beneficial for adapting to stressful situations and tempering immediate and prolonged reactions, and this may be reflected in healthier naturally occurring cortisol profiles. Together, this evidence supports potential bidirectional links between CF and cortisol, however, evidence for such associations during adulthood and old age, and considering both EF and EM remains scant.
The current study
The current study was conducted to examine associations between CF and naturally occurring cortisol levels obtained 3–6 months later using a national sample of adults ranging from 33 to 84 years of age. First, we examined associations between CF and both the MR and the DCS as well as cortisol levels at each of four specific sampling occasions (upon waking, 30-min postwaking, before lunch, and before bed). Second, given the links between cortisol and the frontal lobes and hippocampus, we examined whether EF and EM function were each uniquely related to naturally occurring daily cortisol. Consistent with previous literature, we hypothesized that higher CF would be associated with MR and DCSs. Similarly, higher CF would be associated with higher cortisol levels upon waking and 30-min postwaking but lower levels before lunch and bed. Finally, given links between cortisol receptors in both the frontal lobes and the hippocampus, we expected EF and EM function to both exhibit unique associations with cortisol.