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 regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD).


METHODS
The aim of the present study was to evaluate the levels of circulating 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 allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h.


RESULTS
Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol 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 both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. 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 neurosteroids in the regulation of cognitive function.
Bernardi
F
F
Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy.
Lanzone
A
A
Cento
R M
RM
Spada
R S
RS
Pezzani
I
I
Genazzani
A D
AD
Luisi
S
S
Luisi
M
M
Petraglia
F
F
Genazzani
A R
AR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D019540:Area Under Curve; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone; D003687:Dehydroepiandrosterone / Q000097:blood*; D015140:Dementia, Vascular / Q000097:blood*; D005260:Female; D018757:GABA Modulators / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011280:Pregnanolone / Q000097:blood*
D018757:GABA Modulators; D003687:Dehydroepiandrosterone; D003346:Corticotropin-Releasing Hormone; D011280:Pregnanolone; D006854:Hydrocortisone