Pharmacological modulation of cortisol secretion and dexamethasone suppression in Alzheimer's disease

We have investigated the dexamethasone suppression of cortisol release in a group of 28 patients with senile dementia of the Alzheimer type (SDAT) after stimulation by physostigmine and clonidine, as compared with basal conditions. All patients but one had previously been evaluated with a depression symptom checklist and had submitted to a standard Dexamethasone Suppression Test (DST). SDAT patients showed normal baseline cortisol values measured at 4:00 PM. DST was reproducible, but nonsuppression did not appear to be a feature of the disease, nor of the dementia syndrome, although a majority of the most demented patients were found to be nonsuppressors. Physostigmine stimulated cortisol secretion in 20 of 24 cases, irrespective of the severity of dementia. Clonidine induced a secretion in 12 of 15 cases, but this was less than that observed after cholinergic stimulation. Physostigmine made cortisol release significantly less sensitive to the suppressive effect of dexamethasone than clonidine in SDAT. This double response should be tested as a possible predictor of a cholinergic therapeutic effect.