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Meta‐analysis of early nonmotor features and risk factors for Parkinson disease
Alastair J. Noyce, Jonathan P. Bestwick, Laura Silveira‐Moriyama and 4 more
Annals of Neurology · 2012 · Meta-analysis
Abstract
Objective: To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population‐based screening. Methods: A systematic review and meta‐analysis of risk factors for PD. Results: The strongest associations with later diagnosis of PD were found for having a first‐degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.10–3.57), constipation (relative risk [RR], 2.34; 95% CI, 1.55–3.53), or lack of smoking history (current vs never: RR, 0.44; 95% CI, 0.39–0.50), each at least doubling the risk of PD. Further positive significant associations were found for history of anxiety or depression, pesticide exposure, head injury, rural living, beta‐blockers, farming occupation, and well‐water drinking, and negative significant associations were found for coffee drinking, hypertension, nonsteroidal anti‐inflammatory drugs, calcium channel blockers, and alcohol, but not for diabetes mellitus, cancer, oral contraceptive pill use, surgical menopause, hormone replacement therapy, statins, acetaminophen/paracetamol, aspirin, tea drinking, history of general anesthesia, or gastric ulcers. In the systematic review, additional associations included negative associations with raised serum urate, and single studies or studies with conflicting results. Interpretation: The strongest risk factors associated with later PD diagnosis are having a family history of PD or tremor, a history of constipation, and lack of smoking history. Further factors also but less strongly contribute to risk of PD diagnosis or, as some premotor symptoms, require further standardized studies to demonstrate the magnitude of risk associated with them. ANN NEUROL 2012
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References 56
- 1.
de Lau LML, Giesbergen PCLM, de Rijk MC, et al. Incidence of parkinsonism and Parkinson disease in a general population: the Rotterdam Study. Neurology. 2004;63:1240-1244.
Not in our library10.1212/01.wnl.0000140706.52798.be
- 2.
Driver JA, Logroscino G, Gaziano JM, Kurth T. Incidence and remaining lifetime risk of Parkinson disease in advanced age. Neurology. 2009;72:432-438.
Not in our library10.1212/01.wnl.0000341769.50075.bb
- 3.
Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson's disease. Annu Rev Neurosci. 1999;22:123-144.
Not in our library10.1146/annurev.neuro.22.1.123
- 4.
Gonera EG, van't Hof M, Berger HJ, et al. Symptoms and duration of the prodromal phase in Parkinson's disease. Mov Disord. 1997;12:871-876.
Not in our library10.1002/mds.870120607
- 5.
Hawkes CH. The prodromal phase of sporadic Parkinson's disease: does it exist and if so how long is it? Mov Disord. 2008;23:1799-1807.
Not in our library10.1002/mds.22242
- 6.
Savica R, Rocca WA, Ahlskog JE. When does Parkinson disease start? Arch Neurol. 2010;67:798-801.
Not in our library10.1001/archneurol.2010.135
- 7.
Siderowf A, Stern MB. Premotor Parkinson's disease: clinical features, detection, and prospects for treatment. Ann Neurol. 2008;64(suppl 2):S139-S147.
Not in our library10.1002/ana.21462
- 8.
Tolosa E, Gaig C, Santamaría J, Compta Y. Diagnosis and the premotor phase of Parkinson disease. Neurology. 2009;72(suppl 7):S12-S20.
Not in our library10.1212/wnl.0b013e318198db11
- 9.
Allam MF, Del Castillo AS, Navajas RF-C. Parkinson's disease, smoking and family history: meta-analysis. Eur J Neurol. 2003;10:59-62.
Not in our library10.1046/j.1468-1331.2003.00512.x
- 10.
Allam MF, Campbell MJ, Del Castillo AS, Navajas RF-C. Parkinson's disease protects against smoking? Behav Neurol. 2004;15:65-71.
Not in our library10.1155/2004/516302
- 11.
Allam MF, Campbell MJ, Hofman A, et al. Smoking and Parkinson's disease: systematic review of prospective studies. Mov Disord. 2004;19:614-621.
Not in our library10.1002/mds.20029
- 12.
Bajaj A, Driver JA, Schernhammer ES. Parkinson's disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control. 2010;21:697-707.
Not in our library10.1007/s10552-009-9497-6
- 13.
- 14.
Etminan M, Gill SS, Samii A. Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis. Lancet Neurol. 2005;4:362-365.
Not in our library10.1016/s1474-4422(05)70097-1
- 15.
Gagne JJ, Power MC. Anti-inflammatory drugs and risk of Parkinson disease: a meta-analysis. Neurology. 2010;74:995-1002.
Not in our library10.1212/wnl.0b013e3181d5a4a3
- 16.
Hernán MA, Takkouche B, Caamano-Isorna F, Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann Neurol. 2002;52:276-284.
Not in our library10.1002/ana.10277
- 17.
Ishihara L, Brayne C. A systematic review of depression and mental illness preceding Parkinson's disease. Acta Neurol Scand. 2006;113:211-220.
Not in our library10.1111/j.1600-0404.2006.00579.x
- 18.
Li AA, Mink PJ, McIntosh LJ, et al. Evaluation of epidemiologic and animal data associating pesticides with Parkinson's disease. J Occup Environ Med. 2005;47:1059-1087.
Not in our library10.1097/01.jom.0000174294.58575.3e
- 19.
Priyadarshi A, Khuder SA, Schaub EA, Shrivastava S. A meta-analysis of Parkinson's disease and exposure to pesticides. Neurotoxicology. 2000;21:435-440.
Not in our library
- 20.
Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS. Environmental risk factors and Parkinson's disease: a meta-analysis. Environ Res. 2001;86:122-127.
Not in our library10.1006/enrs.2001.4264
- 21.
Ritz B, Ascherio A, Checkoway H, et al. Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol. 2007;64:990-997.
Not in our library10.1001/archneur.64.7.990
- 22.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
Not in our library10.1136/bmj.b2535
- 23.
Green S, McDonald S. Cochrane Collaboration: more than systematic reviews? Intern Med J. 2005;35:3-4.
Not in our library10.1111/j.1445-5994.2004.00747.x
- 24.
McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863-1872.
Not in our library10.1212/01.wnl.0000187889.17253.b1
- 25.
Wells G, Shea B, O'connell D. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2003.
Not in our library
- 26.
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-560.
Not in our library10.1136/bmj.327.7414.557
- 27.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188.
Not in our library10.1016/0197-2456(86)90046-2
- 28.
Egger M, Smith GD, Phillips AN. Meta-analysis: principles and procedures. BMJ. 1997;315:1533-1537.
Not in our library10.1136/bmj.315.7121.1533
- 29.
Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455-463.
Not in our library10.1111/j.0006-341x.2000.00455.x
- 30.
O'Sullivan SS, Williams DR, Gallagher DA, et al. Nonmotor symptoms as presenting complaints in Parkinson's disease: a clinicopathological study. Mov Disord. 2008;23:101-106.
Not in our library10.1002/mds.21813
- 31.
Nalls MA, Plagnol V, Hernandez DG, et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377:641-649.
Not in our library10.1016/s0140-6736(10)62345-8
- 32.
Tanner CM, Goldman SM, Aston DA, et al. Smoking and Parkinson's disease in twins. Neurology. 2002;58:581-588.
Not in our library10.1212/wnl.58.4.581
- 33.
Wirdefeldt K, Gatz M, Pawitan Y, Pedersen NL. Risk and protective factors for Parkinson's disease: a study in Swedish twins. Ann Neurol. 2005;57:27-33.
Not in our library10.1002/ana.20307
- 34.
Quik M. Smoking, nicotine and Parkinson's disease. Trends Neurosci. 2004;27:561-568.
Not in our library10.1016/j.tins.2004.06.008
- 35.
Fratiglioni L, Wang HX. Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies. Behav Brain Res. 2000;113:117-120.
Not in our library10.1016/s0166-4328(00)00206-0
- 36.
Morens DM, Grandinetti A, Davis JW, et al. Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease. Am J Epidemiol. 1996;144:400-404.
Not in our library10.1093/oxfordjournals.aje.a008941
- 37.
Ragonese P, Salemi G, Morgante L, et al. A case-control study on cigarette, alcohol, and coffee consumption preceding Parkinson's disease. Neuroepidemiology. 2003;22:297-304.
Not in our library10.1159/000071193
- 38.
Grandinetti A, Morens DM, Reed D, MacEachern D. Prospective study of cigarette smoking and the risk of developing idiopathic Parkinson's disease. Am J Epidemiol. 1994;139:1129-1138.
Not in our library10.1093/oxfordjournals.aje.a116960
- 39.
Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219:979-980.
Not in our library10.1126/science.6823561
- 40.
Parker HL. Traumatic encephalopathy (‘Punch Drunk’) of professional pugilists. J Neurol Psychopathol. 1934;15:20-28.
Not in our library10.1136/jnnp.s1-15.57.20
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