Stronger pharmacological cortisol suppression and anticipatory cortisol stress response in transient global amnesia

Abstract

Transient global amnesia (TGA) is a disorder characterized by a sudden attack of severe anterograde memory disturbance that is frequently preceded by emotional or physical stress and resolves within 24 h. By using MRI following the acute episode in TGA patients, small lesions in the hippocampus have been observed. Hence, it has been hypothesized that the disorder is caused by a stress-related transient inhibition of memory formation in the hippocampus. To study the factors that may link stress and TGA, we measured the cortisol day-profile, the dexamethasone feedback inhibition and the effect of experimental exposure to stress on cortisol levels (using the socially evaluated cold pressor test and a control procedure) in 20 patients with a recent history of TGA and in 20 healthy controls. We used self-report scales of depression, anxiety and stress, and a detailed neuropsychological assessment to characterize our collective. We did not observe differences in mean cortisol levels in the cortisol day-profile between the two groups. After administration of low-dose dexamethasone, TGA patients showed significantly stronger cortisol suppression in the daytime profile compared to the control group (p = 0.027). The mean salivary cortisol level was significantly higher in the TGA group prior to and after the experimental stress exposure (p = 0.008 and 0.010 respectively), as well as prior to and after the control condition (p = 0.022 and 0.024, respectively). The TGA group had higher scores of depressive symptomatology (p = 0.021) and anxiety (p = 0.007), but the groups did not differ in the neuropsychological assessment. Our findings of a stronger pharmacological suppression and higher cortisol levels in anticipation of experimental stress in participants with a previous TGA indicate a hypersensitivity of the HPA axis. This suggests that an individual stress sensitivity might play a role in the pathophysiology of TGA.

Keywords: cortisol; hippocampus; memory; stress; transient global amnesia.

Figure 1

Hippocampal MRI in TGA patients. Representative diffusion-weighted MR images after the acute episode of TGA in 16 of the 20 patients. Slice positioning parallel to the long axis of the hippocampus. Yellow arrows indicate the hippocampal lesions.

Figure 2

Cortisol profiles. (A) Daytime profile of salivary cortisol levels. Twenty-four-hour cortisol profile in 20 participants with a history of TGA and 20 age and sex matched controls. Although the cortisol awakening response is higher in the TGA group, this is not significant (p = 0.140). (B) Salivary cortisol levels after dexamethasone challenge. Twenty-four-hour cortisol profile in 20 participants with a history of TGA and 20 age and sex matched controls following the administration of 0.5 mg dexamethasone at 11 p.m. on the day before. TGA patients show a significantly stronger cortisol suppression in the daytime profile compared to the control group (p = 0.027). Data are presented as the mean (in nmol/l) at predefined sample times (awakening, +15, +30, +45, +60 min, thereafter daytime profile) across subjects. * indicates significant group difference.

Figure 3

Cortisol response to experimental stressor. Salivary cortisol response (in nmol/l) to the socially evaluated cold pressor test (A) and the control procedure with warm water (B) in 20 participants with a history of TGA and 20 normal controls. Data are presented as mean ± standard error of the mean. *Indicates significant group difference.