IC-P1-035: Lower cortisol awakening response is associated with smaller hippocampal volumes

Abstract

Background: Although it has frequently been hypothesized that high levels of glucorticoids have deleterious effects on the hippocampus and may contribute to increased risk for Alzheimer’s disease, this study is among the first to investigate the effect of changes in HPA axis activity on hippocampal volume by assessing the diurnal cortisol profile. Methods: Within the SMART-MR study, a prospective cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 278 patients (mean age 62 9 years) with available data on cortisol and hippocampal volume. Circadian cortisol rhythm was assessed with 6 saliva samples, collected at awakening and 30, 45 and 60 minutes thereafter, and at 10 PM and 11 PM. A low dose of dexamethasone (0.5 mg) was administered at 11 PM and saliva was sampled the next morning at awakening. The diurnal cortisol profile was defined as the cortisol awakening response (CAR), a distinct and dynamic part of the cortisol circadian rhythm (mean cortisol secreted within the first hour after awakening); resting evening values (mean of the two evening measurements); and the suppressibility of the HPA axis (cortisol after 0.5 mg dexamethasone). Volumetric measurements of the hippocampus was performed on a 3-dimensional TFE T1-weighted MRI scan with isotropic voxels. The left and right hippocampus were manually traced and corrected for head size by dividing hippocampal volume by intracranial volume, which was obtained by automatic brain segmentation. Results: Mean total hippocampal volume relative to intracranial volume was 6.2 0.7 ml. Linear regression analyses, adjusted for age and sex, showed that subjects with a lower CAR had smaller hippocampal volumes ( per nmol*h/l increase 0.014 ml; 95% CI 0.001 to 0.028). Evening levels and cortisol levels after dexamethasone were not significantly associated with hippocampal volume. Conclusions: In this population, a lower cortisol awakening response was associated with smaller hippocampal volumes, but evening cortisol levels and cortisol levels after dexamethasone suppression were not. Future studies should determine to what extent lower cortisol secretion after awaking associated with smaller hippocampal volumes increases risk for Alzheimer’s disease.