Plasma catecholamine and cardiovascular responses to physostigmine in Alzheimer's disease and aging.
Stimulation of brain cholinergic systems increases activity of both the sympathoneural (SN) and sympathoadrenomedullary (SAM) components of the peripheral sympathetic nervous system. Because presynaptic cholinergic neuron numbers are substantially reduced in Alzheimer's disease (AD), we predicted decreased responsiveness in AD of plasma norepinephrine (NE), an estimate of SN activity, and of epinephrine (EPI), an estimate of SAM activity, to central cholinergic stimulation by the cholinesterase inhibitor physostigmine (0.0125 mg/kg i.v.). Because previous studies have demonstrated that normal human aging increases SN activity but not SAM activity, we specifically hypothesized: (1) a smaller NE response to physostigmine in subjects with mild to moderate AD (n=11; age 72+/-2 yrs; mini-mental state exam [MMSE] scores of 19+/-2) than in healthy older subjects (n=20; age 71+/-1 yrs); and (2) a smaller EPI response in AD subjects than in either healthy older or healthy young subjects (n=9; age 27+/-2 yrs). Unexpectedly, the plasma NE increase following physostigmine only achieved significance in AD subjects and plasma EPI responses were greater in both AD and older subjects than in young subjects. Blood pressure responses to physostigmine were consistent with the catecholamine responses. These data suggest that the presence of mild to moderate AD increases the SN response to cholinergic stimulation and that both AD and normal aging increase the SAM response to cholinergic stimulation. As a result, plasma catecholamine responses to physostigmine do not appear to be useful peripheral neuroendocrine estimates of the severity of brain cholinergic deficits in mild to moderate AD.
Petrie
E C
EC
Mental Health Service (S-116), Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA. petrie.eric@seattle.va.gov
Peskind
E R
ER
Dobie
D J
DJ
Veith
R C
RC
Raskind
M A
MA
D000313:Adrenal Medulla / Q000294:innervation; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D001143:Arousal / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D004837:Epinephrine / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010830:Physostigmine; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D010830:Physostigmine; D009638:Norepinephrine; D004837:Epinephrine