Hypothalamic-pituitary-adrenocortical axis responses to physostigmine: effects of Alzheimer's disease and gender.
We asked whether hypothalamic-pituitary-adrenocortical (HPA) axis responses to a cholinergic stimulus are blunted in patients with Alzheimer's disease (AD) of mild to moderate severity. Such a finding would be consistent with a central cholinergic deficiency early in the course of AD. To address this question, we measured the plasma adrenocorticotropic hormone (ACTH), beta-endorphin-like immunoreactivity (beta E-LI), and cortisol responses to the cholinesterase inhibitor physostigmine in 10 healthy normal older subjects (age = 71 +/- 2 years) and 11 outpatients with probable AD (age = 72 +/- 2 years; Mini Mental State Exam score = 19 +/- 2). Cortisol concentrations were higher in AD subjects throughout the study, but AD and normal older subjects had similar robust ACTH, beta E-LI, and cortisol responses to physostigmine. In all subjects combined, women had greater ACTH, beta E-LI, and cortisol responses to physostigmine than did men. Plasma physostigmine concentrations did not differ between groups. These results suggest that female gender enhances the magnitude of HPA axis responses to cholinergic stimulation in older humans; however, the HPA axis response to physostigmine does not appear to reflect central cholinergic deficiency in the early stages of AD.
Peskind
E R
ER
Geriatric Research, Education, and Clinical Center, Seattle WA 98108, USA.
Raskind
M A
MA
Wingerson
D
D
Pascualy
M
M
Thal
L J
LJ
Dobie
D J
DJ
Wilkinson
C W
CW
D000305:Adrenal Cortex Hormones / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000502:physiology; D002800:Cholinesterase Inhibitors; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008609:Mental Status Schedule; D010830:Physostigmine; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D012016:Reference Values; D012737:Sex Factors; D001615:beta-Endorphin / Q000097:blood
D000305:Adrenal Cortex Hormones; D002800:Cholinesterase Inhibitors; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D010830:Physostigmine; D006854:Hydrocortisone