Peskind E R, Wingerson D, Murray S, Pascualy M, Dobie D J, Le Corre P, Le Verge R, Veith R C, Raskind M A
Geriatric Research Education and Clinical Center, Seattle (Wash), American Lake Veterans Affairs Medical Center, USA.
Arch Gen Psychiatry. 1995 Sep;52(9):774-82. doi: 10.1001/archpsyc.1995.03950210068012.
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 post-mortem locus ceruleus neuronal loss that is reported in patients with AD.
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.
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.
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.
阿尔茨海默病（AD）患者静息脑脊液（CSF）中去甲肾上腺素浓度未发生变化甚至有所升高。这些体内研究结果似乎与AD患者尸检时发现的蓝斑神经元丢失情况不一致。
通过比较盐酸育亨宾、盐酸可乐定和安慰剂给药后AD门诊患者以及老年和青年正常受试者脑脊液中去甲肾上腺素浓度，评估AD和高龄对中枢神经系统去甲肾上腺素能状态的影响。在脑脊液和血浆样本中测量育亨宾及其代谢产物11-羟基育亨宾以及可乐定的水平。通过对简明精神病评定量表中的紧张、兴奋和焦虑项目进行评分来量化行为反应。
盐酸育亨宾引起的脑脊液去甲肾上腺素浓度升高在AD患者和正常老年受试者中均高于正常青年受试者。盐酸可乐定引起的脑脊液去甲肾上腺素浓度降低在各组之间无差异。AD患者服用盐酸育亨宾后的行为唤醒程度高于其他组。
正常老年受试者中枢神经系统去甲肾上腺素能反应性增强，且这种年龄效应在AD患者中依然存在。AD患者对中枢神经系统去甲肾上腺素能活性增加的行为敏感性增强。
