Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia

Objective: Neurosteroids have been suggested to be involved in the regulati on of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopreg nanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occur s in both senile (Alzheimer's disease: AD) and vascular dementia (VD). Design: The aim of the present study was to evaluate the levels of circulat ing allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD. Methods: Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and a llopregnanolone, DHEA and cortisol levels were measured every 15 min for 2 h. Results: Mean +/- S.E.M. allopregnanolone and DHEA basal levels were signif icantly lower in AD and VD than in controls, while cortisol levels were sig nificantly higher than in controls (P<0.01). Allopregnanolone and DHEA leve ls increase in response to CRF test in all subjects but the area under curv e (AUC) in patients was significantly lower than in controls (P<0.01). Cort isol secretion appeared to be very sensitive in response to CRF stimulation : in fact, cortisol response to CRF: test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01). Conclusions: The present study firstly showed that allopregnanolone levels are reduced buth in AD and in VD and that dementia has a preserved stimulat ed response of allopregnanolone to CRE Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurostero ids in the regulation of cognitive function.