EFFECTS OF ALZHEIMERS-DISEASE AND NORMAL AGING ON CEREBROSPINAL-FLUIDNOREPINEPHRINE RESPONSES TO YOHIMBINE AND CLONIDINE

Background: The resting cerebrospinal fluid (CSF) norepinephrine conce ntration is unchanged or even increased in patients with Alzheimer's d isease (AD). These in vivo findings appear to be inconsistent with the postmortem locus ceruleus neuronal loss that is reported in patients with AD. Methods: The effects of AD and advanced age on central nervou s system noradrenergic status were estimated by comparing CSF norepine phrine concentrations following the administration of yohimbine hydroc hloride, clonidine hydrochloride, and placebo in outpatients with AD a nd older and young normal subjects. Levels of yohimbine, its metabolit e 11-hydroxy-yohimbine, and clonidine were measured in CSF and plasma samples. Behavioral responses were quantified by rating the Tension, E xcitement, and Anxiety items on the Brief Psychiatric Rating Scale. Re sults: Yohimbine-induced increases of CSF norepinephrine concentration s were greater in both patients with AD and normal older subjects than in normal young subjects. Clonidine-induced decreases of CSF norepine phrine concentrations did not differ among groups. Behavioral arousal following the administration of yohimbine was greater in patients with AD than in the other groups. Conclusions: Central nervous system nora drenergic responsiveness is enhanced in normal older subjects, and thi s age effect is retained in patients with AD. Behavioral sensitivity t o increased central nervous system noradrenergic activity is enhanced in patients with AD.