The present study is the first to examine the association between baseline deposition of cortisol in hair and change in memory performance in CAD patients undertaking exercise. We saw an improvement in verbal memory performance after exercise, consistent with previous findings [5
], but patients with higher baseline hair cortisol secretion showed less improvement over one year of CR. The association between higher cortisol and less verbal memory improvement persisted even when controlling for depression and perceived stress.
Hair cortisol concentrations in the high cortisol group of the present study (262.8
ng/g)) were comparable to those reported previously (median (full range) = 295.3
ng/g)) during hospital admission for acute MI [8
]. Patients included in the present study were referred to the CR program at least six weeks after MI, which may account for a proportion of patients with lower cortisol concentrations in the present study.
A large body of evidence shows associations between higher cortisol concentrations and both atrophy of the hippocampus, the brain region subserving verbal memory [31
], and memory impairment [33
]. Exposure to stress hormones can lead to a reduction in neuronal health and survival, especially in the hippocampus [34
]. In response to chronic stress, neurons undergo morphological changes, which have a deleterious impact on brain plasticity [35
] and adult hippocampal neurogenesis [36
]. Animal studies have shown that cortisol can decrease the availability of neurotrophic factors such as the brain-derived neurotrophic factor in the hippocampus [36
]. The present finding that high cortisol attenuated improvements in memory scores over the course of a one-year exercise intervention would be consistent with this suggestion.
In a post-hoc
analysis, we explored CABG as an additional covariate since the incidence of CABG was significantly different between the normal and high cortisol groups. Despite existing evidence of cognitive changes after CABG [37
], CABG was not a significant predictor of change in memory performance in this study. Some studies have implicated irregularities in HPA axis function, specifically alterations in the cortisol negative feedback mechanism, in postoperative cognitive deficits [38
], and this would be consistent with the persistence of a trend for higher cortisol predicting changes in memory performance even when controlling for CABG.
An additional post-hoc analysis suggested that the relationship between cortisol and change in verbal memory performance might be modified by cardiopulmonary fitness at baseline; subjects with higher cortisol and poorer fitness entering CR improved significantly less. Further investigations are needed to clarify the potentially bidirectional relationships between physical activity and cortisol concentrations and their effects on cognition.
This study was strengthened by a prospective design, by the use of a noninvasive measure of long-term cortisol and by the use of a highly sensitive instrument to assess verbal memory. This study was limited by a small sample size, restricting the number of covariates; however, no differences in possible confounders between cortisol groups were detected, with the exception of surgical history, which was not associated with verbal memory changes in this population. Practice effects may have contributed to the overall improvement in verbal memory; however, a one-year interval between testing would be expected to minimize such effects on tests of verbal learning and memory [40
]. Furthermore, normal and high cortisol groups were equally subject to possible practice effects. Data were not available on those who declined to participate in the study to assess recruitment bias beyond comparison with an unselected sample. Possible selection biases associated with CR referral, study recruitment, and CR completion might further limit the generalizability of the results. Some patients were unavailable for follow-up cardiopulmonary testing precluding longitudinal fitness assessment. Changes in maximal oxygen uptake may have offered further insight into the effects of cortisol on the contribution of exercise to cognitive changes. Future studies might examine the impact of exercise on cortisol concentrations.