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 attention deficits which are improved by nicotine administration. The importance of measuring multiple abilities in future drug studies is emphasized and results are discussed in terms of nicotine's actions on attention, information processing and short-term memory.
Similar content being viewed by others
References
Araujo D, Lapchak P, Collier B, Quirion S (1988) Characterization of N-[3H] methylcarbamylcholine binding sites and the effect of N-methylcarbamylcholine on acetylcholine release in rat brain. J Neurochem 51:292–299
Brazell MP, Mitchell SN, Joseph MH, Gray JA (1990) Acute administration of nicotine increases the in vivo extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid and ascorbic acid preferentially in the nucleus accumbens of the rat: comparison with caudate-putamen. Neuropharmacology 29:1177–1185
Brazell MP, Mitchell SN, Gray JA (1991) Effect of acute administration of nicotine on in vivo release of noradrenaline in the hippocampus of freely moving rats: A dose-response and antagonist study. Neuropharmacology 30:823–833
Broks P, Preston C, Traub P, Poppleton P, Ward C, Stahl SM (1988) Modelling dementia; effects of scopolamine on memory and attention. Neuropsychologia 28[5]:685–700
Clarke P, Hamill G, Nadi N, Jacobowitz D, Pert A (1986) 3H-Nicotine and 125 I-alpha-bungarotoxin labelled nicotine receptors in the interpeduncular nucleus of rats. II. Effects of habenular deafferentation. J Comp Neurol 251:407–413
Dunnett SB (1985) Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats. Psychopharmacology 87:357–363
Hasenfratz M, Michel C, Nil R, Battig K (1989) Can smoking increase attention in rapid information processing during noise? Electrocortical, physiological and behavioural effects. Psychopharmacology 98:75–80
Hinton D, Sadun A, Blanks J, Miller C (1986) Optic nerve degeneration in Alzheimer's disease. N Engl J Med 315[8]:485–487
Hodges H, Allen Y, Sinden J, Lantos PL, Gray JA (1990) Cholinergic-rich foetal transplants improve cognitivie deficits in lesioned rats, but exacerbate response to cholinergic drugs. Prog Brain Res 82:347–358
Hodges H, Allen Y, Sinden J, Mitchell SN, Arendt T, Lantos PL, Gray JA (1991) The effects of cholinergic drugs and cholinergic-rich foetal neural transplants on alcohol induced deficits in radial maze performance in rats. Behav Brain Res 43:7–28
Hughes CP, Berg L, Danziger WL, Cohen LA, Martin RL (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 40:566–572
Jones GMM (1990) The cholinergic hypothesis of dementia: the effects of lecithin and nicotine on human memory and attention. Doctoral thesis for the University of London, UK
Jones GMM, Reith M, Philpot MP, Sahakian BJ (1987) Smoking and dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry 50:1383
Katz B, Rimmer S (1989) Ophthalmologic manifestations of Alzheimer's disease. Surv Ophthalmol 34:31–43
Loeb M, Alluisi E (1984) Theories of Vigilance. In: Loeb M, Alluisi E (eds) Sustained attention in human performance. Wiley, Chichester, pp 179–395
MacNab M, Folz E, Sweitzer J (1985) Evaluation of signal detection theory on the effects of psychotropic drugs on critical flicker-fusion frequency in normal subjects. Psychopharmacology 85:431–435
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS/ADRDA work group under the auspices of the Department of Health and Human Services Task force on Alzheimer's Disease. Neurology 34:939–944
McNicol D (1972) A primer of signal detection. Allen & Unwin, London
Mash DC, Flynn DD, Potter LT (1985) Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. Science 228:1115–1117
Nelson H (1982) National Adult Reading Test (NART) manual. NFER-Nelson, Windsor
Newhouse P, Sunderland T, Tariot P, Blumhardt C, Weingartner H, Mellow W (1988) Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology 95:171–175
Perry EK, Perry RH, Smith CJ, Purohit J, Bonham P, Dick D, Candy J, Edwardson JA, Fairburn A (1986) Cholinergic receptors in cognitive disorders. Can J Neurol Sci 13:521–527
Perry EK, Perry RH, Smith CJ, Dick DJ, Candy JM, Edwardson JA, Fairburn A, Blessed G (1987) Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases. J Neurol, Neurosurg Psychiatry 50:806–809
Philpot MP, Levy R (1987) A memory clinic for the early diagnosis of dementia. Int J Geriatr Psychiatry 2:195–200
Royal College of Physicians (1983) Smoking or Health. Pitman Med, London
Richard J, Araujo DM, Quirion R (1989) Modulation of cortical acetylcholine release by cholinergic agents. Soc Neurosci Abstr 15[2]:1197
Russell M, Jarvis M, Jones G, Feyerabend C (1990) Nonsmokers show acute tolerance to subcutaneous nicotine. Psychopharmacology 102:56–58
Sahakian BJ (1988) Cholinergic drugs and human cognitive performance. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 20, Psychopharmacology of the aging nervous system. Plenum Press, London
Sahakian B, Jones G, Levy R, Gray J, Warburton D (1989) The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry 154:797–800
Sahgal A (1987a) Contrasting effects of vasopressin, desglycinamide-vasopressin and amphetamine on a delayed matching to position task in rats. Psychopharmacology 93:243–249
Sahgal A (1987b) Some limitations of indices derived from signal detection theory: evaluation of an alternative index for measuring bias in memory tasks. Psychopharmacology 91:517–520
Smith JM, Misiak H (1976) Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects — a review. Psychopharmacology 47:175–182
van Duijn C, Hofman A (1991) Relation between nicotine intake and Alzheimer's disease. Br Med J 302:1491–1494
Warburton D (1986) A state model for mental effort. In: Hockey GR, Gaillard AW, Coles MG (eds) Energetics of human information processing. Martinus Mijhof, Dordrecht, Netherlands, pp 217–232
Warburton D (1988) Psychopharmacological aspects of nicotine. In: Russell M, Stolerman I, Wonnacott S (eds) Nicotine: actions and medical implications. Oxford University Press, Oxford, pp 119–131
Warburton D (1989) Nicotine: an addictive substance or a therapeutic agent? Prog Drug Res 435:9–41
Wechsler D (1955) WAIS manual. Psychological Corporation, NY
Wesnes K, Warburton DM (1984) Effects of scopolamine and nicotine on human rapid information processing performance. Psychopharmacology 82:147–150
West RJ, Jarvis MJ (1986) Effects of nicotine on finger tapping rate in non smokers. Pharmacol Biochem Behav 25:727–731
Wonnacott S, Russell MAH, Stolerman IP (1990) Nicotine psychopharmacology: molecular, cellular and behavioural aspects. Oxford Scientific Publications, Oxford University Press, Oxford
Zilles K (1990) Codistribution of receptors in the human cerebral cortex. In: Mendelsohn FAO, Paxinos G (eds) Receptors in the human nervous system. Academic Press, London
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jones, G.M.M., Sahakian, B.J., Levy, R. et al. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in alzheimer's disease. Psychopharmacology 108, 485–494 (1992). https://doi.org/10.1007/BF02247426
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02247426