Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in alzheimer's disease

Abstract

This single-blind, placebo controlled study reports on the effects of administering three acute doses of nicotine (0.4, 0.6 and 0.8 mg) subcutaneously to a group of Alzheimer's disease (DAT) patients (n = 22), young adult controls (n = 24), and normal aged controls (n = 24). The study extends our previous findings obtained using smaller groups of subjects. Drug effects were examined on three computerised tests: the first measuring rapid visual information processing, sustained visual attention and reaction time (RVIP task); a delayed response matching to location-order task measuring sustained visual attention and visual short-term memory (DRMLO task); and a finger tapping test measuring simple reaction time (FT task). The critical flicker fusion test (CFF) was used as a measure of perception and the WAIS digit span forwards (DS), of auditory short-term memory. Tests were graded in difficulty, titrated to avoid floor and ceiling effects so that meaningful, direct comparisons between groups could be made. Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task--both ascending and descending thresholds). Nicotine administration did not improve auditory and visual short-term memory. There were no consistent, overall patterns of difference in performance between smokers and non-smokers in the control groups, or between males and females in any group. Despite the absence of change in memory functioning, these results demonstrate that DAT patients have significant perceptual and visual attentional deficits which are improved by nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive Enhancing Properties and Tolerability of Cholinergic Agents in Mice: A Comparative Study of Nicotine, Donepezil, and SIB-1553A, a Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors

“…Although substantial loss of cholinergic neurons has been demonstrated in AD (Francis et al, 1999), post-mortem studies have shown that some functional nAChRs remain, even at a late stage of the disease (Shimohama et al, 1986;Whitehouse et al, 1986;Schroder et al, 1991;Court et al, 2001;Perry et al, 2001). In agreement with this observation, nicotine, the nonselective prototypical ligand for nAChRs, improves certain cognitive functions in AD patients (Jones et al, 1992;Wilson et al, 1995;White and Levin, 1999;Newhouse et al, 2001;Rezvani and Levin, 2001). Unfortunately, nicotine also exhibits a broad spectrum of undesirable side effects (Benowitz, 1986;Watkins et al, 2000), which limits its use as a therapy.…”

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

“…Nicotine administration may just be relieving withdrawal and correcting those deficits. However, if low-dose nicotine is administered to normal nonsmokers, thereby avoiding the confound of withdrawal, there is enhanced performance on the continuous performance test with decreased errors of omission without an increase in errors of commission [62] In Alzheimer's disease, where nicotinic cholinergic receptors are known to be decreased in the cortex and hippocampus [63,64], nicotine injections or nicotine skin patches significantly improve attention, learning and memory [65,66,67,68,69,70]. Similarly, in adults with attention deficit disorder, nicotine skin patch reduces clinical symptoms and increases reaction time, but does not improve errors of omission in the Continuous Performance Test [71].…”

Fear-Potentiated Startle to Threat, and Prepulse Inhibition Among Young Adult Nonsmokers, Abstinent Smokers, and Nonabstinent Smokers

“…The results of most studies reveal that smokers report alleviation of negative affect by smoking, (Brandon and Baker 1991) and increased anxiety during withdrawal. Nicotine also has a stimulant effect on cognitive processes, improving vigilance, enhancing selective attention, and promoting response inhibition to irrelevant stimuli (Jones et al 1992). …”