THE EFFECTS OF THYROTROPIN-RELEASING-HORMONE AND SCOPOLAMINE IN ALZHEIMERS-DISEASE AND NORMAL VOLUNTEERS

被引:22
作者
MOLCHAN, SE
MELLOW, AM
HILL, JL
WEINGARTNER, H
MARTINEZ, R
VITIELLO, B
SUNDERLAND, T
机构
[1] NIMH, CLIN SCI LAB, GERIATR PSYCHOPHARMACOL UNIT, BETHESDA, MD 20892 USA
[2] UNIV MICHIGAN, DEPT PSYCHIAT, ANN ARBOR, MI 48109 USA
[3] NIMH, CLIN SCI LAB, BIOSTAT UNIT, BETHESDA, MD 20892 USA
[4] NIAAA, COGNIT NEUROSCI SECT, BETHESDA, MD USA
关键词
THYROTROPIN-RELEASING HORMONE (TRH); NEUROPEPTIDE; SCOPOLAMINE; MEMORY; ALZHEIMERS DISEASE; AGING;
D O I
10.1177/026988119200600404
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Thyrotropin-releasing hormone (TRH), a neuromodulator and possibly a neurotransmitter in the central nervous system, was shown in a prior study of young normal volunteers to attenuate the memory impairment induced by the anticholinergic drug scopolamine. In the present study, the cognitive, behavioral and physiologic effects of high dose TRH (0.5 mg/kg), both alone and following administration of scopolamine, were examined in 10 Alzheimer's disease (AD) patients (mean age +/- SD=63.5 years) and 12 older normal volunteers (mean age=64.9 +/- 8.8 years). On the day AD subjects received TRH alone, modest but statistically significant improvement from baseline performance was documented on some tests of learning and memory, especially in those with mild dementia severity. In comparing cognitive test performance between the scopolamine alone and scopolamine+TRH conditions, only two test scores were significantly higher in the latter condition. In the group of older volunteers, TRH did not attenuate scopolamine-induced cognitive impairment, contrary to prior findings in a group of younger controls. In fact, older subjects performed worse after receiving scopolamine followed by TRH than after receiving scopolamine alone. In addition, no change from baseline cognitive performance was detected after subjects received TRH alone. These findings raise several questions and speculations on possible age-related changes in the cholinergic system, as well as on the mechanism of the interaction of TRH with the cholinergic system.
引用
收藏
页码:489 / 500
页数:12
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