Neurology, Vol 45, Issue 6 1041-1051, Copyright © 1995 by American Academy of Neurology

VIEWS & REVIEWS

Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue?

DM Morens, A Grandinetti, D Reed, LR White and GW Ross
Department of Public Health Sciences, School of Public Health, University of Hawaii, Honolulu 96822, USA.

We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.

This article has been cited by other articles:

				R. Inzelberg and J. Jankovic Are Parkinson disease patients protected from some but not all cancers? Neurology, October 9, 2007; 69(15): 1542 - 1550. [Abstract] [Full Text] [PDF]

				B. Ritz, A. Ascherio, H. Checkoway, K. S. Marder, L. M. Nelson, W. A. Rocca, G. W. Ross, D. Strickland, S. K. Van Den Eeden, and J. Gorell Pooled Analysis of Tobacco Use and Risk of Parkinson Disease Arch Neurol, July 1, 2007; 64(7): 990 - 997. [Abstract] [Full Text] [PDF]

				E. L. Thacker, E. J. O'Reilly, M. G. Weisskopf, H. Chen, M. A. Schwarzschild, M. L. McCullough, E. E. Calle, M. J. Thun, and A. Ascherio Temporal relationship between cigarette smoking and risk of Parkinson disease Neurology, March 6, 2007; 68(10): 764 - 768. [Abstract] [Full Text] [PDF]

				S. Dick, S. Semple, F. Dick, and A. Seaton Occupational titles as risk factors for Parkinson's disease Occup. Med., January 1, 2007; 57(1): 50 - 56. [Abstract] [Full Text] [PDF]

				T. Bordia, N. Parameswaran, H. Fan, J. W. Langston, J. M. McIntosh, and M. Quik Partial Recovery of Striatal Nicotinic Receptors in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Monkeys with Chronic Oral Nicotine J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 285 - 292. [Abstract] [Full Text] [PDF]

				M. Quik, L. Chen, N. Parameswaran, X. Xie, J. W. Langston, and S. E. McCallum Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates. J. Neurosci., April 26, 2006; 26(17): 4681 - 4689. [Abstract] [Full Text] [PDF]

				M. Quik and J. M. McIntosh Striatal {alpha}6* Nicotinic Acetylcholine Receptors: Potential Targets for Parkinson's Disease Therapy J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 481 - 489. [Abstract] [Full Text] [PDF]

				A.C. Williams, L.S. Cartwright, and D.B. Ramsden Parkinson's disease: the first common neurological disease due to auto-intoxication? QJM, March 1, 2005; 98(3): 215 - 226. [Abstract] [Full Text] [PDF]

				C W. Olanow Manganese-Induced Parkinsonism and Parkinson's Disease Ann. N.Y. Acad. Sci., March 1, 2004; 1012(1): 209 - 223. [Abstract] [Full Text] [PDF]

				A. Ascherio and H. Chen Caffeinated clues from epidemiology of Parkinson's disease Neurology, December 9, 2003; 61(90116): S51 - 54. [Full Text]

				N. Castagnoli Jr., J. P. Petzer, S. Steyn, K. Castagnoli, J.-F. Chen, M. A. Schwarzschild, and C. J. Van der Schyf Monoamine oxidase B inhibition and neuroprotection: Studies on selective adenosine A2A receptor antagonists Neurology, December 9, 2003; 61(90116): S62 - 68. [Abstract] [Full Text]

				S M Rosso, E-J Landweer, M Houterman, L Donker Kaat, C M van Duijn, and J C van Swieten Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study J. Neurol. Neurosurg. Psychiatry, November 1, 2003; 74(11): 1574 - 1576. [Abstract] [Full Text] [PDF]

				J. S. Fowler, J. Logan, G.-J. Wang, N. D. Volkow, F. Telang, W. Zhu, D. Franceschi, N. Pappas, R. Ferrieri, C. Shea, et al. Inaugural Article: Low monoamine oxidase B in peripheral organs in smokers PNAS, September 30, 2003; 100(20): 11600 - 11605. [Abstract] [Full Text] [PDF]

				M. Quik, J. D. Sum, P. Whiteaker, S. E. McCallum, M. J. Marks, J. Musachio, J. M. Mcintosh, A. C. Collins, and S. R. Grady Differential Declines in Striatal Nicotinic Receptor Subtype Function after Nigrostriatal Damage in Mice Mol. Pharmacol., May 1, 2003; 63(5): 1169 - 1179. [Abstract] [Full Text] [PDF]

				B.M. Ravina, S.C. Fagan, R.G. Hart, C.A. Hovinga, D.D. Murphy, T.M. Dawson, and J.R. Marler Neuroprotective agents for clinical trials in Parkinson's disease: A systematic assessment Neurology, April 22, 2003; 60(8): 1234 - 1240. [Abstract] [Full Text] [PDF]

				A. Siderowf and M. Stern Update on Parkinson Disease Ann Intern Med, April 15, 2003; 138(8): 651 - 658. [Abstract] [Full Text] [PDF]

				F.-M. Zhou, C. Wilson, and J. A. Dani Muscarinic and Nicotinic Cholinergic Mechanisms in the Mesostriatal Dopamine Systems Neuroscientist, February 1, 2003; 9(1): 23 - 36. [Abstract] [PDF]

				G. Nicholson, A. C. Pereira, and G. M. Hall Parkinson's disease and anaesthesia Br. J. Anaesth., December 1, 2002; 89(6): 904 - 916. [Abstract] [Full Text] [PDF]

				J. M. Kulak, J. L. Musachio, J. M. McIntosh, and M. Quik Declines in Different beta 2* Nicotinic Receptor Populations in Monkey Striatum after Nigrostriatal Damage J. Pharmacol. Exp. Ther., November 1, 2002; 303(2): 633 - 639. [Abstract] [Full Text] [PDF]

				T Foltynie, S Sawcer, C Brayne, and R A Barker The genetic basis of Parkinson's disease J. Neurol. Neurosurg. Psychiatry, October 1, 2002; 73(4): 363 - 370. [Abstract] [Full Text] [PDF]

				M. A. Hernan, H. Checkoway, R. O'Brien, P. Costa-Mallen, I. De Vivo, G. A. Colditz, D. J. Hunter, K. T. Kelsey, and A. Ascherio MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk of PD Neurology, May 14, 2002; 58(9): 1381 - 1387. [Abstract] [Full Text] [PDF]

				M. A. Schwarzschild, J.-F. Chen, and A. Ascherio Caffeinated clues and the promise of adenosine A2A antagonists in PD Neurology, April 23, 2002; 58(8): 1154 - 1160. [Abstract] [Full Text] [PDF]

				H. Checkoway, K. Powers, T. Smith-Weller, G. M. Franklin, W. T. Longstreth Jr., and P. D. Swanson Parkinson's Disease Risks Associated with Cigarette Smoking, Alcohol Consumption, and Caffeine Intake Am. J. Epidemiol., April 15, 2002; 155(8): 732 - 738. [Abstract] [Full Text] [PDF]

				M. F. Allam, A. Vieregge, M. Sieberer, H. Jacobs, J.M. Hagenah, and P. Vieregge Transdermal nicotine in PD: A randomized, double-blind, placebo-controlled study Neurology, April 9, 2002; 58(7): 1133 - 1133. [Full Text] [PDF]

				J. M. Kulak, J. M. McIntosh, and M. Quik Loss of Nicotinic Receptors in Monkey Striatum after 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment Is Due to a Decline in alpha -Conotoxin MII Sites Mol. Pharmacol., January 1, 2002; 61(1): 230 - 238. [Abstract] [Full Text] [PDF]

				M. Quik, Y. Polonskaya, J. M. Kulak, and J. M. McIntosh Vulnerability of 125I-{alpha}-Conotoxin MII Binding Sites to Nigrostriatal Damage in Monkey J. Neurosci., August 1, 2001; 21(15): 5494 - 5500. [Abstract] [Full Text] [PDF]

				C. W. Olanow, R. L. Watts, and W. C. Koller An algorithm (decision tree) for the management of Parkinson's disease (2001):: Treatment Neurology, June 12, 2001; 56(suppl_5): S1 - S88. [Full Text] [PDF]

				M. D. Benedetti, J. H. Bower, D. M. Maraganore, S. K. McDonnell, B. J. Peterson, J. E. Ahlskog, D. J. Schaid, and W. A. Rocca Smoking, alcohol, and coffee consumption preceding Parkinson's disease: A case-control study Neurology, November 14, 2000; 55(9): 1350 - 1358. [Abstract] [Full Text] [PDF]

				P. Costa-Mallen, L. G Costa, T. Smith-Weller, G. M Franklin, P. D Swanson, and H. Checkoway Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism J. Neurol. Neurosurg. Psychiatry, October 1, 2000; 69(4): 535 - 537. [Abstract] [Full Text] [PDF]

				N. Vanacore, V. Bonifati, G. Fabbrini, C. Colosimo, R. Marconi, D. Nicholl, U. Bonuccelli, F. Stocchi, P. Lamberti, G. Volpe, et al. Smoking habits in multiple system atrophy and progressive supranuclear palsy Neurology, January 11, 2000; 54(1): 114 - 114. [Abstract] [Full Text] [PDF]

				J. E. Riggs, N. Vanacore, S. Spila-Alegiani, R. Raschetti, and G. Meco Mortality cancer risk in parkinsonian patients: A population-based study Neurology, September 1, 1999; 53(5): 1158 - 1158. [Full Text]

				J. S. Schneider, J. P. Tinker, M. Van Velson, F. Menzaghi, and G. K. Lloyd Nicotinic Acetylcholine Receptor Agonist SIB-1508Y Improves Cognitive Functioning in Chronic Low-Dose MPTP-Treated Monkeys J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 731 - 739. [Abstract] [Full Text]

				J. H. Bower, D. M. Maraganore, S. K. McDonnell, and W. A. Rocca Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990 Neurology, April 1, 1999; 52(6): 1214 - 1214. [Abstract] [Full Text]

				J. M. Gorell, B. A. Rybicki, C. C. Johnson, and E. L. Peterson Smoking and Parkinson's disease: A dose-response relationship Neurology, January 1, 1999; 52(1): 115 - 115. [Abstract] [Full Text] [PDF]

				N. Vanacore, S. Spila-Alegiani, R. Raschetti, and G. Meco Mortality cancer risk in parkinsonian patients: A population-based study Neurology, January 1, 1999; 52(2): 395 - 395. [Abstract] [Full Text]

				G. W. Dalack, D. J. Healy, and J. H. Meador-Woodruff Nicotine Dependence in Schizophrenia: Clinical Phenomena and Laboratory Findings Am J Psychiatry, November 1, 1998; 155(11): 1490 - 1501. [Abstract] [Full Text]

				A. E. Lang and A. M. Lozano Parkinson's Disease- First of Two Parts N. Engl. J. Med., October 8, 1998; 339(15): 1044 - 1053. [Full Text] [PDF]

				G. Defazio, A. Berardelli, G. Abbruzzese, V. Lepore, V. Coviello, D. Acquistapace, L. Capus, F. Carella, M. T. De Berardinis, G. Galardi, et al. Possible risk factors for primary adult onset dystonia: a case-control investigation by the Italian Movement Disorders Study Group J. Neurol. Neurosurg. Psychiatry, January 1, 1998; 64(1): 25 - 32. [Abstract] [Full Text]

				F. Olale, V. Gerzanich, A. Kuryatov, F. Wang, and J. Lindstrom Chronic Nicotine Exposure Differentially Affects the Function of Human alpha 3, alpha 4, and alpha 7 Neuronal Nicotinic Receptor Subtypes J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 675 - 683. [Abstract] [Full Text]

				V. Gerzanich, A. Kuryatov, R. Anand, and J. Lindstrom ""Orphan"" alpha 6 Nicotinic AChR Subunit Can Form a Functional Heteromeric Acetylcholine Receptor Mol. Pharmacol., February 1, 1997; 51(2): 320 - 327. [Abstract] [Full Text] [PDF]

				F. Menzaghi, K. T. Whelan, V. B. Risbrough, T. S. Rao, and G. K. Lloyd Interactions between a Novel Cholinergic Ion Channel Agonist, SIB-1765F and L-DOPA in the Reserpine Model of Parkinson's Disease in Rats J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 393 - 401. [Abstract] [Full Text]

				J. S. Fowler, N. D. Volkow, G.-J. Wang, N. Pappas, J. Logan, C. Shea, D. Alexoff, R. R. MacGregor, D. J. Schlyer, I. Zezulkova, et al. Brain monoamine oxidase A inhibition in cigarette smokers PNAS, November 26, 1996; 93(24): 14065 - 14069. [Abstract] [Full Text] [PDF]