In view of the cholinergic deficits present in patients with Alzheimer's disease (AD), a widely investigated treatment strategy for the cognitive deficits in AD is cholinergic stimulation. Although nicotinic cholinergic receptor binding has been demonstrated to be deficient in the AD brain, the predominant theoretical and therapeutic focus to date has been on muscarinic cholinergic receptors and systems. The purpose of the present study was to evaluate the effects of sustained nicotine administration on behavior, cognition, and physiology. A double-blind placebo-controlled trial was conducted in which six patients with probable AD were exposed to 7, 8, and 7 days of placebo, nicotine, and washout, respectively. Daily sessions evaluating learning, memory, and behavior were conducted. Global cognitive functioning, rest and activity levels, cardiac activity, and blood levels were also measured. Findings included improved learning during the nicotine condition, which persisted throughout washout. Memory, behavior, and global cognition were not significantly affected. Sustained administration of nicotine appeared to be safe, although sleep showed a significant decrease.
Bibliographical noteFunding Information:
The authorsg ratefullya cknowledgeth e assistanceo f Kris Bettin and Pat Gastonguayin collectingd ata,a nd Julie Larson for building the repeateda cquisitiona pparatusT. hey also thankt he nurseso f the IntermediateC are Unit at the Departmenot f VeteransA ffairs Medical Center,M inneapolis,M innesota,w ithoutw hom this studyc ould not haveb eenc onducted,a nd James Cleary for his helpful and insightful commentsT. his researchw as supportedi n part by Lederle Laboratories, who provided the Pros@’ nicotine and placebo patchesa nd funded laboratorya ssessmenotf nicotine and cotinine levels. The work of the first author was supportebdy Grant T32 AGO0198fr om theN ationalI nstituteso f Aging.
- Alzheimer's disease
- Delayed matching to sample
- Repeated acquisition