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November 03, 2020; 95 (18) Article

Risk factors of Parkinson disease

Simultaneous assessment, interactions, and etiologic subtypes

Daniele Belvisi, Roberta Pellicciari, Andrea Fabbrini, Matteo Costanzo, Sara Pietracupa, Maria De Lucia, Nicola Modugno, View ORCID ProfileFrancesca Magrinelli, Carlo Dallocchio, Tommaso Ercoli, Claudio Terravecchia, Alessandra Nicoletti, Paolo Solla, Giovanni Fabbrini, Michele Tinazzi, Alfredo Berardelli, Giovanni Defazio
First published September 17, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010813
Daniele Belvisi
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Roberta Pellicciari
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Andrea Fabbrini
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Matteo Costanzo
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Sara Pietracupa
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Maria De Lucia
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Nicola Modugno
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Francesca Magrinelli
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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  • ORCID record for Francesca Magrinelli
Carlo Dallocchio
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Tommaso Ercoli
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Claudio Terravecchia
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Alessandra Nicoletti
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Paolo Solla
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Giovanni Fabbrini
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Michele Tinazzi
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Alfredo Berardelli
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Giovanni Defazio
From IRCCS Neuromed (D.B., A.F., S.P., M.D.L., N.M., G.F., A.B.), Pozzilli, IS; Department of Basic Medical Sciences, Neuroscience and Sense Organs (R.P.), “Aldo Moro,” University of Bari; Department of Human Neurosciences (D.B., M.C., G.F., A.B.), Sapienza, University of Rome; Department of Neurosciences, Biomedicine and Movement Sciences (F.M., M.T.), University of Verona; Neurology Unit (C.D.), ASST Pavia-Ospedale Civile di Voghera; Department of Medical Sciences and Public Health (T.E., P.S., G.D.), University of Cagliari, Monserrato; and Department G.F. Ingrassia (C.T., A.N.), Neuroscience Section, University of Catania, Italy.
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Citation
Risk factors of Parkinson disease
Simultaneous assessment, interactions, and etiologic subtypes
Daniele Belvisi, Roberta Pellicciari, Andrea Fabbrini, Matteo Costanzo, Sara Pietracupa, Maria De Lucia, Nicola Modugno, Francesca Magrinelli, Carlo Dallocchio, Tommaso Ercoli, Claudio Terravecchia, Alessandra Nicoletti, Paolo Solla, Giovanni Fabbrini, Michele Tinazzi, Alfredo Berardelli, Giovanni Defazio
Neurology Nov 2020, 95 (18) e2500-e2508; DOI: 10.1212/WNL.0000000000010813

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Abstract

Objective To perform a simultaneous evaluation of potential risk/protective factors of Parkinson disease (PD) to identify independent risk/protective factors, to assess interaction among factors, and to determine whether identified risk factors predict etiologic subtypes of PD.

Methods We designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbid conditions, and drugs. The study enrolled 694 patients with PD and 640 healthy controls from 6 neurologic centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis.

Results The simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.4–0.9), smoking (OR 0.7, 95% CI 0.6–0.9), physical activity (OR 0.8, 95% CI 0.7–0.9), family history of PD (OR 3.2, 95% CI 2.2–4.8), dyspepsia (OR 1.8, 95% CI 1.3–2.4), and exposure to pesticides (OR 2.3, 95% CI1.3–4.2), oils (OR 5.6, 95% CI 2.3–13.7), metals (OR 2.8, 95% CI 1.5–5.4), and general anesthesia (OR 6.1, 95% CI 2.9–12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified 4 subtypes with different risk factor profiles. In group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents was present in 30% of patients. In groups 2 and 3, a family history of PD was lacking, while exposure to toxic agents (group 2) and dyspepsia (group 3) played major roles. Group 4 consisted of patients with no risk factors.

Conclusions This study demonstrated that 9 factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same participant.

Glossary

CI=
confidence interval;
NSAID=
nonsteroidal anti-inflammatory drug;
OR=
odds ratio;
PD=
Parkinson disease;
RERI=
relative excess risk due to interaction

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 805

  • CME Course: NPub.org/cmelist

  • Received March 16, 2020.
  • Accepted in final form June 25, 2020.
  • © 2020 American Academy of Neurology
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