Download PDF
Semin Neurol 2022; 42(05): 626-638
DOI: 10.1055/s-0042-1758780
Review Article

Parkinson's Disease: Risk Factor Modification and Prevention

Suraj Rajan
1   Division of Movement Disorders, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
,
Bonnie Kaas
1   Division of Movement Disorders, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
› Author Affiliations Funding None.
› Further Information
    Permissions and Reprints

Abstract

The global burden of Parkinson's disease (PD) has increased from 2.5 to 6.1 million since the 1990s. This is expected to rise as the world population ages and lives longer. With the current consensus on the existence of a prediagnostic phase of PD, which can be divided into a preclinical stage and a prodromal stage, we can better define the risk markers and prodromal markers of PD in the broader context of PD pathogenesis. Here, we review this pathogenetic process, and discuss the evidence behind various heritability factors, exposure to pesticides and farming, high dairy consumption, and traumatic brain injuries that have been known to raise PD risk. Physical activity, early active lifestyle, high serum uric acid, caffeine consumption, exposure to tobacco, nonsteroidal anti-inflammatory drugs, and calcium channel blockers, as well as the Mediterranean and the MIND diets are observed to lower PD risk. This knowledge, when combined with ways to identify at-risk populations and early prodromal PD patients, can help the clinician make practical recommendations. Most importantly, it helps us set the parameters for epidemiological studies and create the paradigms for clinical trials.

Keywords

Parkinson's disease - prevention - risk factors - prodromal Parkinson - pesticides - exercise


Publication History

Article published online:
25 November 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Dorsey ER, Elbaz A, Nichols E. et al; GBD 2016 Parkinson's Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018; 17 (11) 939-953
    CrossrefPubMedSearch in Google Scholar
  • 2 Elbaz A, Bower JH, Maraganore DM. et al. Risk tables for parkinsonism and Parkinson's disease. J Clin Epidemiol 2002; 55 (01) 25-31
    CrossrefPubMedSearch in Google Scholar
  • 3 Postuma RB, Berg D, Stern M. et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015; 30 (12) 1591-1601
    CrossrefPubMedSearch in Google Scholar
  • 4 Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci 2017; 18 (07) 435-450
    CrossrefPubMedSearch in Google Scholar
  • 5 Adler CH, Beach TG. Neuropathological basis of nonmotor manifestations of Parkinson's disease. Mov Disord 2016; 31 (08) 1114-1119
    CrossrefPubMedSearch in Google Scholar
  • 6 Jellinger KA. Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update-I. Hypokinetic-rigid movement disorders. J Neural Transm (Vienna) 2019; 126 (08) 933-995
    CrossrefPubMedSearch in Google Scholar
  • 7 Goedert M, Spillantini MG, Del Tredici K, Braak H. 100 years of Lewy pathology. Nat Rev Neurol 2013; 9 (01) 13-24
    CrossrefPubMedSearch in Google Scholar
  • 8 Gelpi E, Navarro-Otano J, Tolosa E. et al. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov Disord 2014; 29 (08) 1010-1018
    CrossrefPubMedSearch in Google Scholar
  • 9 Beach TG, Adler CH, Sue LI. et al; Arizona Parkinson's Disease Consortium. Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 2010; 119 (06) 689-702
    CrossrefPubMedSearch in Google Scholar
  • 10 Del Tredici K, Rüb U, De Vos RA, Bohl JR, Braak H. Where does Parkinson disease pathology begin in the brain?. J Neuropathol Exp Neurol 2002; 61 (05) 413-426
    CrossrefPubMedSearch in Google Scholar
  • 11 Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 2006; 396 (01) 67-72
    CrossrefPubMedSearch in Google Scholar
  • 12 Iacono D, Geraci-Erck M, Rabin ML. et al. Parkinson disease and incidental Lewy body disease: Just a question of time?. Neurology 2015; 85 (19) 1670-1679
    CrossrefPubMedSearch in Google Scholar
  • 13 Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003; 24 (02) 197-211
    CrossrefPubMedSearch in Google Scholar
  • 14 Kim S, Kwon SH, Kam TI. et al. Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson's disease. Neuron 2019; 103 (04) 627-641.e7
    CrossrefPubMedSearch in Google Scholar
  • 15 Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 2003; 110 (05) 517-536
    Search in Google Scholar
  • 16 Noyce AJ, Lees AJ, Schrag AE. The prediagnostic phase of Parkinson's disease. J Neurol Neurosurg Psychiatry 2016; 87 (08) 871-878
    CrossrefPubMedSearch in Google Scholar
  • 17 Berg D, Postuma RB, Adler CH. et al. MDS research criteria for prodromal Parkinson's disease. Mov Disord 2015; 30 (12) 1600-1611
    CrossrefPubMedSearch in Google Scholar
  • 18 Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 2017; 18 (02) 101-113
    CrossrefPubMedSearch in Google Scholar
  • 19 Ross GW, Petrovitch H, Abbott RD. et al. Association of olfactory dysfunction with risk for future Parkinson's disease. Ann Neurol 2008; 63 (02) 167-173
    CrossrefPubMedSearch in Google Scholar
  • 20 Rey NL, George S, Steiner JA. et al. Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term. Acta Neuropathol 2018; 135 (01) 65-83
    CrossrefPubMedSearch in Google Scholar
  • 21 Rey NL, Bousset L, George S. et al. α-Synuclein conformational strains spread, seed and target neuronal cells differentially after injection into the olfactory bulb. Acta Neuropathol Commun 2019; 7 (01) 221
    CrossrefPubMedSearch in Google Scholar
  • 22 Lau A, So RWL, Lau HHC. et al. α-Synuclein strains target distinct brain regions and cell types. Nat Neurosci 2020; 23 (01) 21-31
    CrossrefPubMedSearch in Google Scholar
  • 23 Borghammer P. The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson's disease: explaining motor asymmetry, non-motor phenotypes, and cognitive decline. J Parkinsons Dis 2021; (Preprint) 1-20
    PubMedSearch in Google Scholar
  • 24 Mahlknecht P, Iranzo A, Högl B. et al; Sleep Innsbruck Barcelona Group. Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology 2015; 84 (07) 654-658
    CrossrefPubMedSearch in Google Scholar
  • 25 Ponsen MM, Stoffers D, Twisk JW, Wolters ECh, Berendse HW. Hyposmia and executive dysfunction as predictors of future Parkinson's disease: a prospective study. Mov Disord 2009; 24 (07) 1060-1065
    CrossrefPubMedSearch in Google Scholar
  • 26 Breen DP, Halliday GM, Lang AE. Gut-brain axis and the spread of α-synuclein pathology: vagal highway or dead end?. Mov Disord 2019; 34 (03) 307-316
    CrossrefPubMedSearch in Google Scholar
  • 27 Pan-Montojo F, Schwarz M, Winkler C. et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2012; 2 (01) 898
    CrossrefPubMedSearch in Google Scholar
  • 28 Liu B, Fang F, Pedersen NL. et al. Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology 2017; 88 (21) 1996-2002
    CrossrefPubMedSearch in Google Scholar
  • 29 Svensson E, Horváth-Puhó E, Thomsen RW. et al. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol 2015; 78 (04) 522-529
    CrossrefPubMedSearch in Google Scholar
  • 30 Boertien JM, Pereira PAB, Aho VTE, Scheperjans F. Increasing comparability and utility of gut microbiome studies in Parkinson's disease: a systematic review. J Parkinsons Dis 2019; 9 (Suppl. 02) S297-S312
    CrossrefPubMedSearch in Google Scholar
  • 31 Elfil M, Kamel S, Kandil M, Koo BB, Schaefer SM. Implications of the gut microbiome in Parkinson's disease. Mov Disord 2020; 35 (06) 921-933
    CrossrefPubMedSearch in Google Scholar
  • 32 Wallen ZD, Appah M, Dean MN. et al. Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. NPJ Parkinsons Dis 2020; 6 (01) 11
    CrossrefPubMedSearch in Google Scholar
  • 33 Gallop A, Weagley J, Paracha SU, Grossberg G. The role of the gut microbiome in Parkinson's disease. J Geriatr Psychiatry Neurol 2021; 34 (04) 253-262
    CrossrefPubMedSearch in Google Scholar
  • 34 Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A. Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis 2021; 7 (01) 1-13
    CrossrefPubMedSearch in Google Scholar
  • 35 Böttner M, Zorenkov D, Hellwig I. et al. Expression pattern and localization of alpha-synuclein in the human enteric nervous system. Neurobiol Dis 2012; 48 (03) 474-480
    CrossrefPubMedSearch in Google Scholar
  • 36 Barber TR, Reading P. Rapid Eye Movement Sleep Behaviour Disorder. Elsevier; 2019. Accessed February 19, 2022 at: https://www.sciencedirect.com/science/article/pii/B9780128093245235402
    PubMed
  • 37 Galbiati A, Verga L, Giora E, Zucconi M, Ferini-Strambi L. The risk of neurodegeneration in REM sleep behavior disorder: a systematic review and meta-analysis of longitudinal studies. Sleep Med Rev 2019; 43: 37-46
    CrossrefPubMedSearch in Google Scholar
  • 38 Boeve BF, Silber MH, Saper CB. et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 2007; 130 (Pt 11): 2770-2788
    CrossrefPubMedSearch in Google Scholar
  • 39 Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson's disease in primary care: a case-control study. Lancet Neurol 2015; 14 (01) 57-64
    CrossrefPubMedSearch in Google Scholar
  • 40 Goldstein DS. Dysautonomia in parkinson disease. In: Comprehensive Physiology. Pollock DM ed, 2014. Available at: https://doi.org/10.1002/cphy.c130026
    CrossrefPubMed
  • 41 Palma JA, Carmona-Abellan MM, Barriobero N. et al. Is cardiac function impaired in premotor Parkinson's disease? A retrospective cohort study. Mov Disord 2013; 28 (05) 591-596
    CrossrefPubMedSearch in Google Scholar
  • 42 Palma JA, Kaufmann H. Autonomic disorders predicting Parkinson's disease. Parkinsonism Relat Disord 2014; 20 (Suppl. 01) S94-S98
    CrossrefPubMedSearch in Google Scholar
  • 43 Berg D, Marek K, Ross GW, Poewe W. Defining at-risk populations for Parkinson's disease: lessons from ongoing studies. Mov Disord 2012; 27 (05) 656-665
    CrossrefPubMedSearch in Google Scholar
  • 44 Noyce AJ, Bestwick JP, Silveira-Moriyama L. et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol 2012; 72 (06) 893-901
    CrossrefPubMedSearch in Google Scholar
  • 45 Keller MF, Saad M, Bras J. et al; International Parkinson's Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2). Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease. Hum Mol Genet 2012; 21 (22) 4996-5009
    CrossrefPubMedSearch in Google Scholar
  • 46 Gao HM, Hong JS. Gene-environment interactions: key to unraveling the mystery of Parkinson's disease. Prog Neurobiol 2011; 94 (01) 1-19
    CrossrefPubMedSearch in Google Scholar
  • 47 González-Aramburu I, Sánchez-Juan P, Jesús S. et al. Genetic variability related to serum uric acid concentration and risk of Parkinson's disease. Mov Disord 2013; 28 (12) 1737-1740
    CrossrefPubMedSearch in Google Scholar
  • 48 Simon KC, Eberly S, Gao X. et al; Parkinson Study Group. Mendelian randomization of serum urate and Parkinson disease progression. Ann Neurol 2014; 76 (06) 862-868
    CrossrefPubMedSearch in Google Scholar
  • 49 Cannon JR, Greenamyre JT. Gene-environment interactions in Parkinson's disease: specific evidence in humans and mammalian models. Neurobiol Dis 2013; 57: 38-46
    CrossrefPubMedSearch in Google Scholar
  • 50 Hamza TH, Chen H, Hill-Burns EM. et al. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee. PLoS Genet 2011; 7 (08) e1002237
    CrossrefPubMedSearch in Google Scholar
  • 51 Hill-Burns EM, Singh N, Ganguly P. et al. A genetic basis for the variable effect of smoking/nicotine on Parkinson's disease. Pharmacogenomics J 2013; 13 (06) 530-537
    CrossrefPubMedSearch in Google Scholar
  • 52 Gao J, Liu R, Zhao E. et al. Head injury, potential interaction with genes, and risk for Parkinson's disease. Parkinsonism Relat Disord 2015; 21 (03) 292-296
    CrossrefPubMedSearch in Google Scholar
  • 53 Petrovitch H, Ross GW, Abbott RD. et al. Plantation work and risk of Parkinson disease in a population-based longitudinal study. Arch Neurol 2002; 59 (11) 1787-1792
    CrossrefPubMedSearch in Google Scholar
  • 54 Ascherio A, Schwarzschild MA. The epidemiology of Parkinson's disease: risk factors and prevention. Lancet Neurol 2016; 15 (12) 1257-1272
    CrossrefPubMedSearch in Google Scholar
  • 55 Ball N, Teo WP, Chandra S, Chapman J. Parkinson's disease and the environment. Front Neurol 2019; 10: 218
    CrossrefPubMedSearch in Google Scholar
  • 56 Ascherio A, Chen H, Weisskopf MG. et al. Pesticide exposure and risk for Parkinson's disease. Ann Neurol 2006; 60 (02) 197-203
    CrossrefPubMedSearch in Google Scholar
  • 57 Goldman SM. Environmental toxins and Parkinson's disease. Annu Rev Pharmacol Toxicol 2014; 54: 141-164
    CrossrefPubMedSearch in Google Scholar
  • 58 Cheng YH, Chou WC, Yang YF. et al. PBPK/PD assessment for Parkinson's disease risk posed by airborne pesticide paraquat exposure. Environ Sci Pollut Res Int 2018; 25 (06) 5359-5368
    CrossrefPubMedSearch in Google Scholar
  • 59 Abbott RD, Ross GW, Petrovitch H. et al. Midlife milk consumption and substantia nigra neuron density at death. Neurology 2016; 86 (06) 512-519
    CrossrefPubMedSearch in Google Scholar
  • 60 Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B. Parkinson's disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 2009; 169 (08) 919-926
    CrossrefPubMedSearch in Google Scholar
  • 61 Liu M, Shin EJ, Dang DK. et al. Trichloroethylene and Parkinson's disease: risk assessment. Mol Neurobiol 2018; 55 (07) 6201-6214
    CrossrefPubMedSearch in Google Scholar
  • 62 Goldman SM. Trichloroethylene and Parkinson's disease: dissolving the puzzle. Expert Rev Neurother 2010; 10 (06) 835-837
    CrossrefPubMedSearch in Google Scholar
  • 63 Perl DP, Olanow CW. The neuropathology of manganese-induced Parkinsonism. J Neuropathol Exp Neurol 2007; 66 (08) 675-682
    CrossrefPubMedSearch in Google Scholar
  • 64 Guilarte TR. Is methamphetamine abuse a risk factor in parkinsonism?. Neurotoxicology 2001; 22 (06) 725-731
    CrossrefPubMedSearch in Google Scholar
  • 65 Gatto NM, Cockburn M, Bronstein J, Manthripragada AD, Ritz B. Well-water consumption and Parkinson's disease in rural California. Environ Health Perspect 2009; 117 (12) 1912-1918
    CrossrefPubMedSearch in Google Scholar
  • 66 Kab S, Spinosi J, Chaperon L. et al. Agricultural activities and the incidence of Parkinson's disease in the general French population. Eur J Epidemiol 2017; 32 (03) 203-216
    CrossrefPubMedSearch in Google Scholar
  • 67 Silvestre GCSB, Ferreira MJM, Figueiredo SEFMR, Silva CALD, Siqueira HH, Silva AMCD. Parkinson disease and occupational and environmental exposure to pesticides in a region of intense agribusiness activity in Brazil: a case-control study. J Occup Environ Med 2020; 62 (12) e732-e737
    CrossrefPubMedSearch in Google Scholar
  • 68 Cagac A. Farming, well water consumption, rural living, and pesticide exposure in early life as the risk factors for Parkinson disease in Igdir province. Neurosciences (Riyadh) 2020; 25 (02) 129-133
    CrossrefPubMedSearch in Google Scholar
  • 69 Taylor KM, Saint-Hilaire MH, Sudarsky L. et al. Head injury at early ages is associated with risk of Parkinson's disease. Parkinsonism Relat Disord 2016; 23: 57-61
    CrossrefPubMedSearch in Google Scholar
  • 70 Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord 2013; 28 (09) 1222-1229
    CrossrefPubMedSearch in Google Scholar
  • 71 Gardner RC, Burke JF, Nettiksimmons J, Goldman S, Tanner CM, Yaffe K. Traumatic brain injury in later life increases risk for Parkinson disease. Ann Neurol 2015; 77 (06) 987-995
    CrossrefPubMedSearch in Google Scholar
  • 72 Paul KC, Chuang YH, Shih IF. et al. The association between lifestyle factors and Parkinson's disease progression and mortality. Mov Disord 2019; 34 (01) 58-66
    CrossrefPubMedSearch in Google Scholar
  • 73 Ahlskog JE. Aerobic exercise: evidence for a direct brain effect to slow Parkinson disease progression. Mayo Clin Proc 2018; 93 (03) 360-372
    CrossrefPubMedSearch in Google Scholar
  • 74 LaHue SC, Comella CL, Tanner CM. The best medicine? The influence of physical activity and inactivity on Parkinson's disease. Mov Disord 2016; 31 (10) 1444-1454
    CrossrefPubMedSearch in Google Scholar
  • 75 Cruise KE, Bucks RS, Loftus AM, Newton RU, Pegoraro R, Thomas MG. Exercise and Parkinson's: benefits for cognition and quality of life. Acta Neurol Scand 2011; 123 (01) 13-19
    CrossrefPubMedSearch in Google Scholar
  • 76 Ridgel AL, Kim CH, Fickes EJ, Muller MD, Alberts JL. Changes in executive function after acute bouts of passive cycling in Parkinson's disease. J Aging Phys Act 2011; 19 (02) 87-98
    CrossrefPubMedSearch in Google Scholar
  • 77 David FJ, Robichaud JA, Leurgans SE. et al. Exercise improves cognition in Parkinson's disease: the PRET-PD randomized, clinical trial. Mov Disord 2015; 30 (12) 1657-1663
    CrossrefPubMedSearch in Google Scholar
  • 78 Fisher BE, Li Q, Nacca A. et al. Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson's disease. Neuroreport 2013; 24 (10) 509-514
    CrossrefPubMedSearch in Google Scholar
  • 79 Chen H, Zhang SM, Schwarzschild MA, Hernán MA, Ascherio A. Physical activity and the risk of Parkinson disease. Neurology 2005; 64 (04) 664-669
    CrossrefPubMedSearch in Google Scholar
  • 80 Logroscino G, Sesso HD, Paffenbarger Jr RSJ, Lee IM. Physical activity and risk of Parkinson's disease: a prospective cohort study. J Neurol Neurosurg Psychiatry 2006; 77 (12) 1318-1322
    CrossrefPubMedSearch in Google Scholar
  • 81 Xu Q, Park Y, Huang X. et al. Physical activities and future risk of Parkinson disease. Neurology 2010; 75 (04) 341-348
    CrossrefPubMedSearch in Google Scholar
  • 82 Yang F, Trolle Lagerros Y, Bellocco R. et al. Physical activity and risk of Parkinson's disease in the Swedish National March Cohort. Brain 2015; 138 (Pt 2): 269-275
    CrossrefPubMedSearch in Google Scholar
  • 83 Fang X, Han D, Cheng Q. et al. Association of levels of physical activity with risk of Parkinson disease: a systematic review and meta-analysis. JAMA Netw Open 2018; 1 (05) e182421
    CrossrefPubMedSearch in Google Scholar
  • 84 Petzinger GM, Holschneider DP, Fisher BE. et al. The effects of exercise on dopamine neurotransmission in Parkinson's disease: targeting neuroplasticity to modulate basal ganglia circuitry. Brain Plast 2015; 1 (01) 29-39
    CrossrefPubMedSearch in Google Scholar
  • 85 Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, Jakowec MW. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease. Lancet Neurol 2013; 12 (07) 716-726
    CrossrefPubMedSearch in Google Scholar
  • 86 Zigmond MJ, Smeyne RJ. Exercise: is it a neuroprotective and if so, how does it work?. Parkinsonism Relat Disord 2014; 20 (Suppl. 01) S123-S127
    CrossrefPubMedSearch in Google Scholar
  • 87 Crotty GF, Schwarzschild MA. Chasing protection in Parkinson's disease: does exercise reduce risk and progression?. Front Aging Neurosci 2020; 12: 186
    CrossrefPubMedSearch in Google Scholar
  • 88 Factor SA, Bennett A, Hohler AD, Wang D, Miyasaki JM. Quality improvement in neurology: Parkinson disease update quality measurement set: executive summary. Neurology 2016; 86 (24) 2278-2283
    CrossrefPubMedSearch in Google Scholar
  • 89 Piercy KL, Troiano RP. Physical activity guidelines for Americans from the US Department of Health and Human Services. Circ Cardiovasc Qual Outcomes 2018; 11 (11) e005263 . Available at:
    CrossrefPubMedSearch in Google Scholar
  • 90 Thacker EL, O'Reilly EJ, Weisskopf MG. et al. Temporal relationship between cigarette smoking and risk of Parkinson disease. Neurology 2007; 68 (10) 764-768
    CrossrefPubMedSearch in Google Scholar
  • 91 Chen H, Huang X, Guo X. et al. Smoking duration, intensity, and risk of Parkinson disease. Neurology 2010; 74 (11) 878-884
    CrossrefPubMedSearch in Google Scholar
  • 92 The NIC-PD-study – A randomized, placebo-controlled, double-blind, multi-centre trial to assess the disease-modifying potential of transdermal nicotine in early Parkinson's disease in Germany and N. America. MDS Abstracts. Accessed May 10, 2021 at: https://www.mdsabstracts.org/abstract/the-nic-pd-study-a-randomized-placebo-controlled-double-blind-multi-centre-trial-to-assess-the-disease-modifying-potential-of-transdermal-nicotine-in-early-parkinsons-disease-in-g/
    PubMed
  • 93 Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson's disease. Parkinsonism Relat Disord 2012; 18 (Suppl. 01) S210-S212
    CrossrefPubMedSearch in Google Scholar
  • 94 Athauda D, Foltynie T. The ongoing pursuit of neuroprotective therapies in Parkinson disease. Nat Rev Neurol 2015; 11 (01) 25-40
    CrossrefPubMedSearch in Google Scholar
  • 95 Chen H, Zhang SM, Hernán MA. et al. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 2003; 60 (08) 1059-1064
    CrossrefPubMedSearch in Google Scholar
  • 96 Chen H, Jacobs E, Schwarzschild MA. et al. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol 2005; 58 (06) 963-967
    CrossrefPubMedSearch in Google Scholar
  • 97 Rees K, Stowe R, Patel S. et al. Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson's disease: evidence from observational studies. Cochrane Database Syst Rev. 2011 (11):CD008454
    PubMedSearch in Google Scholar
  • 98 Wang Q, Liu Y, Zhou J. Neuroinflammation in Parkinson's disease and its potential as therapeutic target. Transl Neurodegener 2015; 4 (01) 19
    CrossrefPubMedSearch in Google Scholar
  • 99 Surmeier DJ, Guzman JN, Sanchez-Padilla J. Calcium, cellular aging, and selective neuronal vulnerability in Parkinson's disease. Cell Calcium 2010; 47 (02) 175-182
    CrossrefPubMedSearch in Google Scholar
  • 100 Ritz B, Rhodes SL, Qian L, Schernhammer E, Olsen JH, Friis S. L-type calcium channel blockers and Parkinson disease in Denmark. Ann Neurol 2010; 67 (05) 600-606
    CrossrefPubMedSearch in Google Scholar
  • 101 Maiti B, Perlmutter JS. A clinical trial of isradipine: What went wrong?. Ann Intern Med 2020; 172 (09) 625-626
    CrossrefPubMedSearch in Google Scholar
  • 102 Venuto CS, Yang L, Javidnia M, Oakes D, James Surmeier D, Simuni T. Isradipine plasma pharmacokinetics and exposure-response in early Parkinson's disease. Ann Clin Transl Neurol 2021; 8 (03) 603-612
    CrossrefPubMedSearch in Google Scholar
  • 103 Gao X, O'Reilly ÉJ, Schwarzschild MA, Ascherio A. Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology 2016; 86 (06) 520-526
    CrossrefPubMedSearch in Google Scholar
  • 104 Schlesinger I, Schlesinger N. Uric acid in Parkinson's disease. Mov Disord 2008; 23 (12) 1653-1657
    CrossrefPubMedSearch in Google Scholar
  • 105 Ascherio A, LeWitt PA, Xu K. et al; Parkinson Study Group DATATOP Investigators. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol 2009; 66 (12) 1460-1468
    CrossrefPubMedSearch in Google Scholar
  • 106 Wen M, Zhou B, Chen YH. et al. Serum uric acid levels in patients with Parkinson's disease: a meta-analysis. PLoS One 2017; 12 (03) e0173731
    CrossrefPubMedSearch in Google Scholar
  • 107 Schwarzschild MA, Ascherio A, Casaceli C. et al; Parkinson Study Group SURE-PD3 Investigators. Effect of urate-elevating inosine on early Parkinson disease progression: the SURE-PD3 randomized clinical trial. JAMA 2021; 326 (10) 926-939
    CrossrefPubMedSearch in Google Scholar
  • 108 Bai S, Song Y, Huang X. et al. Statin use and the risk of Parkinson's disease: an updated meta-analysis. PLoS One 2016; 11 (03) e0152564
    CrossrefPubMedSearch in Google Scholar
  • 109 Gao X, Simon KC, Schwarzschild MA, Ascherio A. Prospective study of statin use and risk of Parkinson disease. Arch Neurol 2012; 69 (03) 380-384
    CrossrefPubMedSearch in Google Scholar
  • 110 Poly TN, Islam MM, Walther BA. et al. Exploring the association between statin use and the risk of Parkinson's disease: a meta-analysis of observational studies. Neuroepidemiology 2017; 49 (3-4): 142-151
    CrossrefPubMedSearch in Google Scholar
  • 111 Yood MU, McCarthy BD, Kempf J. et al. Racial differences in reaching target low-density lipoprotein goal among individuals treated with prescription statin therapy. Am Heart J 2006; 152 (04) 777-784
    CrossrefPubMedSearch in Google Scholar
  • 112 Carroll CB, Wyse RKH. Simvastatin as a potential disease-modifying therapy for patients with Parkinson's disease: rationale for clinical trial, and current progress. J Parkinsons Dis 2017; 7 (04) 545-568
    CrossrefPubMedSearch in Google Scholar
  • 113 Gao X, Chen H, Fung TT. et al. Prospective study of dietary pattern and risk of Parkinson disease. Am J Clin Nutr 2007; 86 (05) 1486-1494
    CrossrefPubMedSearch in Google Scholar
  • 114 Maraki MI, Yannakoulia M, Stamelou M. et al. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson's disease. Mov Disord 2019; 34 (01) 48-57
    CrossrefPubMedSearch in Google Scholar
  • 115 Agarwal P, Wang Y, Buchman AS, Holland TM, Bennett DA, Morris MC. MIND diet associated with reduced incidence and delayed progression of ParkinsonismA in old age. J Nutr Health Aging 2018; 22 (10) 1211-1215
    CrossrefPubMedSearch in Google Scholar
  • 116 Sääksjärvi K, Knekt P, Lundqvist A. et al. A cohort study on diet and the risk of Parkinson's disease: the role of food groups and diet quality. Br J Nutr 2013; 109 (02) 329-337
    CrossrefPubMedSearch in Google Scholar
  • 117 Okubo H, Miyake Y, Sasaki S. et al; Fukuoka Kinki Parkinson's Disease Study Group. Dietary patterns and risk of Parkinson's disease: a case-control study in Japan. Eur J Neurol 2012; 19 (05) 681-688
    CrossrefPubMedSearch in Google Scholar
  • 118 Cassani E, Barichella M, Ferri V. et al. Dietary habits in Parkinson's disease: adherence to Mediterranean diet. Parkinsonism Relat Disord 2017; 42: 40-46
    CrossrefPubMedSearch in Google Scholar
  • 119 Alcalay RN, Gu Y, Mejia-Santana H, Cote L, Marder KS, Scarmeas N. The association between Mediterranean diet adherence and Parkinson's disease. Mov Disord 2012; 27 (06) 771-774
    CrossrefPubMedSearch in Google Scholar
  • 120 Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimers Dement 2015; 11 (09) 1007-1014
    CrossrefPubMedSearch in Google Scholar
  • 121 Metcalfe-Roach A, Yu AC, Golz E. et al. MIND and Mediterranean diets associated with later onset of Parkinson's disease. Mov Disord 2021; 36 (04) 977-984
    CrossrefPubMedSearch in Google Scholar
  • 122 Ross GW, Abbott RD, Petrovitch H. et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000; 283 (20) 2674-2679
    CrossrefPubMedSearch in Google Scholar
  • 123 Ascherio A, Zhang SM, Hernán MA. et al. Prospective study of caffeine consumption and risk of Parkinson's disease in men and women. Ann Neurol 2001; 50 (01) 56-63
    CrossrefPubMedSearch in Google Scholar
  • 124 Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J. Coffee and tea consumption and the risk of Parkinson's disease. Mov Disord 2007; 22 (15) 2242-2248
    CrossrefPubMedSearch in Google Scholar
  • 125 Sääksjärvi K, Knekt P, Rissanen H, Laaksonen MA, Reunanen A, Männistö S. Prospective study of coffee consumption and risk of Parkinson's disease. Eur J Clin Nutr 2008; 62 (07) 908-915
    CrossrefPubMedSearch in Google Scholar
  • 126 Liu R, Guo X, Park Y. et al. Caffeine intake, smoking, and risk of Parkinson disease in men and women. Am J Epidemiol 2012; 175 (11) 1200-1207
    CrossrefPubMedSearch in Google Scholar
  • 127 Qi H, Li S. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease. Geriatr Gerontol Int 2014; 14 (02) 430-439
    CrossrefPubMedSearch in Google Scholar
  • 128 Ren X, Chen JF. Caffeine and Parkinson's disease: multiple benefits and emerging mechanisms. Front Neurosci 2020; 14: 602697
    CrossrefPubMedSearch in Google Scholar
  • 129 Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A. Diet and Parkinson's disease: a potential role of dairy products in men. Ann Neurol 2002; 52 (06) 793-801
    CrossrefPubMedSearch in Google Scholar
  • 130 Park M, Ross GW, Petrovitch H. et al. Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Neurology 2005; 64 (06) 1047-1051
    CrossrefPubMedSearch in Google Scholar
  • 131 Chen H, O'Reilly E, McCullough ML. et al. Consumption of dairy products and risk of Parkinson's disease. Am J Epidemiol 2007; 165 (09) 998-1006
    CrossrefPubMedSearch in Google Scholar
  • 132 Kyrozis A, Ghika A, Stathopoulos P, Vassilopoulos D, Trichopoulos D, Trichopoulou A. Dietary and lifestyle variables in relation to incidence of Parkinson's disease in Greece. Eur J Epidemiol 2013; 28 (01) 67-77
    CrossrefPubMedSearch in Google Scholar
  • 133 Jiang W, Ju C, Jiang H, Zhang D. Dairy foods intake and risk of Parkinson's disease: a dose-response meta-analysis of prospective cohort studies. Eur J Epidemiol 2014; 29 (09) 613-619
    CrossrefPubMedSearch in Google Scholar
  • 134 Miyake Y, Tanaka K, Fukushima W. et al; Fukuoka Kinki Parkinson's Disease Study Group. Lack of association of dairy food, calcium, and vitamin D intake with the risk of Parkinson's disease: a case-control study in Japan. Parkinsonism Relat Disord 2011; 17 (02) 112-116
    CrossrefPubMedSearch in Google Scholar
  • 135 Abbas MM, Xu Z, Tan LCS. Epidemiology of Parkinson's disease - east versus west. Mov Disord Clin Pract (Hoboken) 2017; 5 (01) 14-28
    CrossrefPubMedSearch in Google Scholar
  • 136 Boulos C, Yaghi N, El Hayeck R, Heraoui GN, Fakhoury-Sayegh N. Nutritional risk factors, microbiota and Parkinson's disease: What is the current evidence?. Nutrients 2019; 11 (08) 1896
    CrossrefPubMedSearch in Google Scholar
  • 137 Bettiol SS, Rose TC, Hughes CJ, Smith LA. Alcohol consumption and Parkinson's disease risk: a review of recent findings. J Parkinsons Dis 2015; 5 (03) 425-442
    CrossrefPubMedSearch in Google Scholar
  • 138 Hernán MA, Chen H, Schwarzschild MA, Ascherio A. Alcohol consumption and the incidence of Parkinson's disease. Ann Neurol 2003; 54 (02) 170-175
    CrossrefPubMedSearch in Google Scholar
  • 139 Liu R, Guo X, Park Y. et al. Alcohol consumption, types of alcohol, and Parkinson's disease. PLoS One 2013; 8 (06) e66452
    CrossrefPubMedSearch in Google Scholar
  • 140 Paganini-Hill A. Risk factors for Parkinson's disease: the leisure world cohort study. Neuroepidemiology 2001; 20 (02) 118-124
    CrossrefPubMedSearch in Google Scholar
  • 141 Palacios N, Gao X, O'Reilly E. et al. Alcohol and risk of Parkinson's disease in a large, prospective cohort of men and women. Mov Disord 2012; 27 (08) 980-987
    CrossrefPubMedSearch in Google Scholar
  • 142 Tan LC, Koh WP, Yuan JM. et al. Differential effects of black versus green tea on risk of Parkinson's disease in the Singapore Chinese Health Study. Am J Epidemiol 2008; 167 (05) 553-560
    CrossrefPubMedSearch in Google Scholar
  • 143 Zhang D, Jiang H, Xie J. Alcohol intake and risk of Parkinson's disease: a meta-analysis of observational studies. Mov Disord 2014; 29 (06) 819-822
    CrossrefPubMedSearch in Google Scholar
  • 144 Kim IY, Yang TO, Heath AK. et al; Million Women Study Collaborators. Alcohol intake and Parkinson's disease risk in the million women study. Mov Disord 2020; 35 (03) 443-449
    CrossrefPubMedSearch in Google Scholar
  • 145 de Lau LML, Koudstaal PJ, Witteman JCM, Hofman A, Breteler MMB. Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease. Neurology 2006; 67 (02) 315-318
    CrossrefPubMedSearch in Google Scholar
  • 146 Chen H, Zhang SM, Schwarzschild MA. et al. Folate intake and risk of Parkinson's disease. Am J Epidemiol 2004; 160 (04) 368-375
    CrossrefPubMedSearch in Google Scholar
  • 147 Murakami K, Miyake Y, Sasaki S. et al; Fukuoka Kinki Parkinson's Disease Study Group. Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case-control study in Japan. Br J Nutr 2010; 104 (05) 757-764
    CrossrefPubMedSearch in Google Scholar
  • 148 Hughes KC, Gao X, Kim IY. et al. Intake of antioxidant vitamins and risk of Parkinson's disease. Mov Disord 2016; 31 (12) 1909-1914
    CrossrefPubMedSearch in Google Scholar
  • 149 Morens DM, Grandinetti A, Waslien CI, Park CB, Ross GW, White LR. Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake. Neurology 1996; 46 (05) 1270-1274
    CrossrefPubMedSearch in Google Scholar
  • 150 Ying AF, Khan S, Wu Y. et al. Dietary antioxidants and risk of Parkinson's disease in the Singapore Chinese Health Study. Mov Disord 2020; 35 (10) 1765-1773
    CrossrefPubMedSearch in Google Scholar
  • 151 Yang F, Wolk A, Håkansson N, Pedersen NL, Wirdefeldt K. Dietary antioxidants and risk of Parkinson's disease in two population-based cohorts. Mov Disord 2017; 32 (11) 1631-1636
    CrossrefPubMedSearch in Google Scholar
  • 152 Hantikainen E, Trolle Lagerros Y, Ye W. et al. Dietary antioxidants and the risk of Parkinson disease: the Swedish National March Cohort. Neurology 2021; 96 (06) e895-e903
    CrossrefPubMedSearch in Google Scholar
  • 153 Hellenbrand W, Boeing H, Robra BP. et al. Diet and Parkinson's disease. II: a possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study. Neurology 1996; 47 (03) 644-650
    CrossrefPubMedSearch in Google Scholar
  • 154 de Rijk MC, Breteler MM, den Breeijen JH. et al. Dietary antioxidants and Parkinson disease. The Rotterdam Study. Arch Neurol 1997; 54 (06) 762-765
    CrossrefPubMedSearch in Google Scholar
  • 155 Anderson C, Checkoway H, Franklin GM, Beresford S, Smith-Weller T, Swanson PD. Dietary factors in Parkinson's disease: the role of food groups and specific foods. Mov Disord 1999; 14 (01) 21-27
    CrossrefPubMedSearch in Google Scholar
  • 156 Miyake Y, Fukushima W, Tanaka K. et al; Fukuoka Kinki Parkinson's Disease Study Group. Dietary intake of antioxidant vitamins and risk of Parkinson's disease: a case-control study in Japan. Eur J Neurol 2011; 18 (01) 106-113
    CrossrefPubMedSearch in Google Scholar
  • 157 Scheider WL, Hershey LA, Vena JE, Holmlund T, Marshall JR. Freudenheim. Dietary antioxidants and other dietary factors in the etiology of Parkinson's disease. Mov Disord 1997; 12 (02) 190-196
    CrossrefPubMedSearch in Google Scholar
  • 158 Powers KM, Smith-Weller T, Franklin GM, Longstreth Jr WT, Swanson PD, Checkoway H. Parkinson's disease risks associated with dietary iron, manganese, and other nutrient intakes. Neurology 2003; 60 (11) 1761-1766
    CrossrefPubMedSearch in Google Scholar
  • 159 Logroscino G, Marder K, Cote L, Tang MX, Shea S, Mayeux R. Dietary lipids and antioxidants in Parkinson's disease: a population-based, case-control study. Ann Neurol 1996; 39 (01) 89-94
    CrossrefPubMedSearch in Google Scholar
  • 160 Tanaka K, Miyake Y, Fukushima W. et al; Fukuoka Kinki Parkinson's Disease Study Group. Intake of Japanese and Chinese teas reduces risk of Parkinson's disease. Parkinsonism Relat Disord 2011; 17 (06) 446-450
    CrossrefPubMedSearch in Google Scholar
  • 161 Lv Z, Qi H, Wang L. et al. Vitamin D status and Parkinson's disease: a systematic review and meta-analysis. Neurol Sci 2014; 35 (11) 1723-1730
    CrossrefPubMedSearch in Google Scholar
  • 162 Zhou Z, Zhou R, Zhang Z, Li K. The association between vitamin D status, vitamin D supplementation, sunlight exposure, and Parkinson's disease: a systematic review and meta-analysis. Med Sci Monit 2019; 25: 666-674
    CrossrefPubMedSearch in Google Scholar
  • 163 Luo X, Ou R, Dutta R, Tian Y, Xiong H, Shang H. Association between serum vitamin D levels and Parkinson's disease: a systematic review and meta-analysis. Front Neurol 2018; 9: 909
    CrossrefPubMedSearch in Google Scholar
  • 164 Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M. Serum vitamin D and the risk of Parkinson disease. Arch Neurol 2010; 67 (07) 808-811
    CrossrefPubMedSearch in Google Scholar
  • 165 Shrestha S, Lutsey PL, Alonso A, Huang X, Mosley Jr TH, Chen H. Serum 25-hydroxyvitamin D concentrations in mid-adulthood and Parkinson's disease risk. Mov Disord 2016; 31 (07) 972-978
    CrossrefPubMedSearch in Google Scholar
  • 166 Dong J, Beard JD, Umbach DM. et al. Dietary fat intake and risk for Parkinson's disease. Mov Disord 2014; 29 (13) 1623-1630
    CrossrefPubMedSearch in Google Scholar
  • 167 Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A. Dietary intakes of fat and risk of Parkinson's disease. Am J Epidemiol 2003; 157 (11) 1007-1014
    CrossrefPubMedSearch in Google Scholar
  • 168 Abbott RD, Ross GW, White LR. et al. Environmental, life-style, and physical precursors of clinical Parkinson's disease: recent findings from the Honolulu-Asia Aging Study. J Neurol 2003; 250 (0, Suppl 3) III30-III39
    CrossrefPubMedSearch in Google Scholar
  • 169 de Lau LML, Bornebroek M, Witteman JCM, Hofman A, Koudstaal PJ, Breteler MMB. Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study. Neurology 2005; 64 (12) 2040-2045
    CrossrefPubMedSearch in Google Scholar
  • 170 Qu Y, Chen X, Xu MM, Sun Q. Relationship between high dietary fat intake and Parkinson's disease risk: a meta-analysis. Neural Regen Res 2019; 14 (12) 2156-2163
    CrossrefPubMedSearch in Google Scholar
  • 171 Savitt JM, Dawson VL, Dawson TM. Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 2006; 116 (07) 1744-1754
    CrossrefPubMedSearch in Google Scholar
  • 172 Klein C, Westenberger A. Genetics of Parkinson's disease. Cold Spring Harb Perspect Med 2012; 2 (01) a008888
    CrossrefPubMedSearch in Google Scholar
  • 173 American Heart Association, ( n.d. ). American Heart Association Recommendations for Physical Activity in Adults and Kids. Accessed February 6, 2022 at: Updated 2018 https://www.heart.org/en/healthy-living/fitness/fitness-basics/aha-recs-for-physical-activity-in-adults
    PubMed