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

Abstract

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.

Cerebrospinal Fluid Epinephrine in Alzheimer's Disease and Normal Aging

“…Concentrations of yohimbine and its active metabolite 11-hydroxy-yohimbine in CSF and plasma in these subjects have been reported previously (Peskind et al 1995). In summary, neither the total concentrations of yohimbine plus its active metabolite 11-hydroxy yohimbine nor the concentrations of clonidine differed among groups in either CSF or plasma.…”

“…Effects of these pharmacologic agents on agitation and blood pressure also were measured. CSF norepinephrine concentrations determined in these studies have been reported previously (Peskind et al 1995;Elrod et al 1997).…”

“…The radioenzymatic assay for EPI also was the same as described in Study 1. CSF and plasma concentrations of yohimbine and its active metabolite, 11-hydroxy-yohimbine, and clonidine have been reported previously (Peskind et al 1995;Le Corre et al 1997). Agitation was quantified by summing scores on the Tension, Excitement, and Anxiety items of the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962).…”

Antipsychotic drugs for psychosis and agitation in dementia: efficacy, safety, and a possible noradrenergic mechanism of action

“…When LC NE outflow is stimulated by yohimbine, AD patients demonstrate robust CSF NE increases that are equivalent to those of normal older patients and substantially greater than in young patients (Peskind et al, 1995); AD patients, but not normal older or young patients, developed agitation symptoms following yohimbine. Studies in postmortem brain tissue demonstrate compensatory changes in brain noradrenergic systems consistent with these clinical research findings.…”

“…Results of postmortem brain tissue and clinical studies from our laboratory help resolve this paradox (Peskind et al, 1995;Elrod et al, 1997;Szot et al, 2006;Wang et al, 2009).…”