Summary
Subjects with Down syndrome exhibit various types of cognitive impairment. Neuropathological and neurochemical studies revealed similarities between Down syndrome and Alzheimer’s disease, cholinergic deficits being the most consistent findings. To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5–31 years) received placebo and a single dose of transdermal nicotine (5mg patch) over 2h in a single-blind, within-subjects repeated measures design. Auditory event-related potentials (ERPs) and neuropsychological tests, comprising digit symbol performance subtest from WAIS-R and the Frankfurt Attention Inventory (FAIR) were performed. Effects of nicotine administration in Down syndrome individuals were a decrease of ERP-P3 latency in 7 of 8 subjects (electrode position Cz: 386.9 ± 24.0ms vs. 363.1 ± 26.9.2 ms, placebo vs. nicotine, respectively; P = 0.058) and an increase of ERP-P3 amplitude in 6 of 8 subjects (electrode position Cz: 17.4 ± 5.5 vs. 18.0 ± 4.5μV, placebo vs. nicotine respectively; P = 0.725). Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Brioni JD, Decker MW, Sullivan JP, Arneric SP (1997) The pharmacology of (-)-nicotine and novel cholinergic channel modulators. Adv Pharmacol 39: 191–220
Diaz F, Zurron M (1995) Auditory evoked potentials in Down’s syndrome. Electroencephalogr Clin Neurophysiol 96: 526–537
Dursun SM, Revely MA, Bird R, Stirton F (1994) Longasting improvement of Tourette’s syndrome with transdermal nicotine. Lancet 344: 1577
French SJ, Humby T, Horner CH, Sofroniew MV, Rattray M (1999) Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine. Mol Brain Res 67: 124–136
Frodl-Bauch T, Bottlender R, Hegerl U (1999) Neurochemical substrates and neuroana-tomical generators of the event-related P300. Neuropsychobiol 40: 86–94
Gray R, Rajan AS, Radcliffe KA, Yakehiro M, Dani JA (1996) Hippocampal synaptic transmission enhanced by low concentration of nicotine. Nature 383: 713–716
Haxby JV (1989) Neuropsychological evaluation of adults with Down’s syndrome: patterns of selective impairment in nondemented old adults. J Ment Defic Res 33: 193–200
Jones GMM, Sahakian BJ, Levy R, Warburton DM, Gray JA (1992) Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer’s disease. Psychopharmacology 108: 485–494
Kihara T, Shimohama S, Urushitani M, Sawada H, Kimura J, Kume T, Maeda T, Akaike A (1998) Stimulation of alpha 4 beta 2 nicotinic acetylcholine receptors inhibits betaamyloid toxicity. Brain Res 792: 331–334
Kish S, Karlinsky H, Becker L, Gilbert J, Rebbetoy M, Chang LJ, DiStefano L, Hornykiewicz O (1989) Down’s syndrome individuals begin life with normal levels of brain cholinergic markers. J Neurochem 52: 1183–1187
Kishnani PS, Sullivan JA, Walter BK, Spiridigliozzi GA, Doraiswamy PM, Krishnan KRR (1999) Cholinergic therapy for Down’s syndrome. Lancet 353: 1064–1065
Knott VJ, Harr A, Ilivitsky V (1999) Separate and combined effecst of scopolamine and mecamylamine on human event-related brain potentials. Hum Psychopharmacol Clin Exp 14: 307–317
Lawrence AD, Sahakian BJ (1998) The cognitive psychopharmacology of Alzheimer’s disease: focus on cholinergic systems. Neurochem Res 23: 787–794
Lincoln AJ, Courchesne E, Kilman BA, Galambos R (1986) Auditory ERPs and information processing in Down’s syndrome children. In: McCallum WC, Zappoli Z, Denoth F (eds) Cerebral psychophysiology: studies in event-related potentials. Electroencephalogr Clin Neurophysiol [Suppl] 38: 492–495
Marks MJ, Stitzel JA, Collins AC (1985) Time course study of the effects of chronic nicotine infusion on drug response and brain receptors. J Pharmacol Exp Ther 235: 619–628
McGehee DS, Heath MJS, Gelber S, Devay P, Role LW (1995) Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 269: 1692–1696
Melyn MA, White DT (1973) Mental and developmental milestones of noninstitu-tionalized Down’s syndrome children. Pediatrics 52: 542–548
Moosbrugger H, Oehlschlägel J (1996) FAIR Frankfurter Aufmerksamkeits-Inventar. Hans Huber, Bern
Newhouse PA, Potter A, Levin ED (1997) Nicotinic systems and Alzheimer’s disease: implications for therapeutics. Drugs Aging 11: 206–228
Nordberg A, Lundquist H, Hartvig P, Liljy A, Langström B (1995) Kinetic analysis of regional (S)(-)11C-Nicotinic binding in normal and Alzheimer brains-in vivo assessment using positron emission tomography. Alz Dis Assoc Disord 9: 21–27
Parks RW, Becker RE, Rippey RF, Gilbert DG, Matthews JR, Kabatay E, Young CS, Vohs C, Danz V, Keim P, Collins GT, Zigler SS, Urycki PG (1996) Increased regional cerebral glucose metabolism and semantic memory performance in Alzheimer’s disease: a pilot double blind transdermal nicotine positron emission tomography study. Neuropsychol Rev 6: 61–79
Perry EK, Morris CM, Court JA, Cheng A, Fairbairn AF, McKeith IG, Irving D, Brown A, Perry RH (1995) Alteration in nicotine binding sites in Parkinson’s disease, Lewy body dementia and Alzheimer’s disease: possible index of early neuropathology. Neuroscience 64: 385–395
Polich J (1996) Meta-analysis of P300 normative aging studies. Psychophysiology 33: 334–353
Prendergast MA, Buccafusco JJ (1998) (-)-Nicotine increases mRNA encoding G3PDH and the vesicular acetylcholine transporter in vivo. Neuroreport 9: 1261–1265
Rowell PP, Maureen L (1997) Dose-response relationship for nicotine-induced up-regulation of rat brain nicotine receptors. J Neurochem 68: 1982–1989
Rowell PP, Duggan DS (1998) Long-lasting inactivation of nicotine receptor function in vitro by treatment with concentrations of nicotine. Neuropharmacology 37: 103–111
Snaedal J, Johannesson T, Jonsson JE, Gylfadottir G (1996) The effects of nicotine in dermal plaster on cognitive functions in patients with Alzheimer’s disease. Dementia 7: 47–52
St. Clair DF, Blackwood D (1985) Premature senility in Down’s syndrome. Lancet Jul 6:34
Teller JK, Russo C, DeBusk LM, Angelini G, Zaccheo D, Dagna-Bricarelli F, Scartezzini P, Bertolini S, Mann DM, Tabaton M, Gambetti P (1996) Presence of soluble amyloid B-peptide precedes amyloid plaque formation in Down’s syndrome. Nat Med 2: 93–95
Tewes U (1991) Hamburg-Wechsler Intelligenztest für Erwachsene / Revision 1991. Hans Huber, Bern
Vieregge P, Verleger R, Schulze-Rava H, Kömpf D (1992) Late cognitive event-related in adult Down’s syndrome. Biol Psychiatry 32: 1118–1134
White HK, Levin ED (1999) Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacol 143: 158–165
Wilson AL, Langley LK, Monley J, Bauer T, Rottunda S, McFalls E, Kovera C, McCarten JR (1995) Nicotine patches in Alzheimer’s disease: pilot study on learning, memory,and safety. Pharmacol Biochem Behav 51: 509–514
Wisniewski KE, Kida E (1994) Abnormal neurogenesis and synaptogenesis in Down syndrome brain. Dev Brain Dysfunct 7: 289–301
Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 17: 278–282
Yates CM, Simpson J, Maloney AFJ, Gordon A, Reid AH (1980) Alzheimer-like cholinergic deficiency in Down’s syndrome. Lancet 2(8201): 979
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag/Wien
About this chapter
Cite this chapter
Bernert, G., Sustrova, M., Sovcikova, E., Seidl, R., Lubec, G. (2001). Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. In: Lubec, G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_19
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6262-0_19
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83704-7
Online ISBN: 978-3-7091-6262-0
eBook Packages: Springer Book Archive