September 1995

Effects of Alzheimer's Disease and Normal Aging on Cerebrospinal Fluid Norepinephrine Responses to Yohimbine and Clonidine

Author Affiliations

From the Geriatric Research Education and Clinical Center, Seattle (Wash)/American Lake Veterans Affairs Medical Center (Drs Peskind, Pascualy, Dobie, Veith, and Raskind and Ms Murray), the Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Drs Peskind, Wingerson, Pascualy, Dobie, Veith, and Raskind and Ms Murray), and the Faculte des Sciences Pharmaceutiqueset Biologiques, University of Rennes I (France) (Drs Le Corre and Le Verge).

Arch Gen Psychiatry. 1995;52(9):774-782. doi:10.1001/archpsyc.1995.03950210068012

Background:  The resting cerebrospinal fluid (CSF) norepinephrine concentration is unchanged or even increased in patients with Alzheimer's disease (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 nervous system noradrenergic status were estimated by comparing CSF norepinephrine concentrations following the administration of yohimbine hydrochloride, clonidine hydrochloride, and placebo in outpatients with AD and older and young normal subjects. Levels of yohimbine, its metabolite 11-hydroxy-yohimbine, and clonidine were measured in CSF and plasma samples. Behavioral responses were quantified by rating the Tension, Excitement, and Anxiety items on the Brief Psychiatric Rating Scale.

Results:  Yohimbine-induced increases of CSF norepinephrine concentrations were greater in both patients with AD and normal older subjects than in normal young subjects. Clonidine-induced decreases of CSF norepinephrine 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 noradrenergic responsiveness is enhanced in normal older subjects, and this age effect is retained in patients with AD. Behavioral sensitivity to increased central nervous system noradrenergic activity is enhanced in patients with AD.