Belvisi Daniele, Pellicciari Roberta, Fabbrini Andrea, Costanzo Matteo, Pietracupa Sara, De Lucia Maria, Modugno Nicola, Magrinelli Francesca, Dallocchio Carlo, Ercoli Tommaso, Terravecchia Claudio, Nicoletti Alessandra, Solla Paolo, Fabbrini Giovanni, Tinazzi Michele, Berardelli Alfredo, Defazio Giovanni
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.
Neurology. 2020 Nov 3;95(18):e2500-e2508. doi: 10.1212/WNL.0000000000010813. Epub 2020 Sep 17.
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.
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.
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.
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.
同时评估帕金森病（PD）的潜在风险/保护因素，以确定独立的风险/保护因素，评估因素之间的相互作用，并确定已识别的风险因素是否能预测PD的病因亚型。
我们设计了一项大型病例对照研究，评估31个PD的保护/风险因素，包括环境和生活方式因素、合并症和药物。该研究从6个神经科中心招募了694例PD患者和640名健康对照。数据通过逻辑回归模型、相加交互作用模型和聚类分析进行分析。
对31个假定的PD风险/保护因素进行同时评估显示，只有咖啡饮用（比值比[OR]0.6；95%置信区间[CI]0.4 - 0.9）、吸烟（OR 0.7，95% CI 0.6 - 0.9）、体育活动（OR 0.8，95% CI 0.7 - 0.9）、PD家族史（OR 3.2，95% CI 2.2 - 4.8）、消化不良（OR 1.8，95% CI 1.3 - 2.4）以及接触杀虫剂（OR 2.3，95% CI 1.3 - 4.2）、油类（OR 5.6，95% CI 2.3 - 13.7）、金属（OR 2.8，95% CI 1.5 - 5.4）和全身麻醉（OR 6.1，95% CI 2.9 - 12.7）与PD独立相关。没有证据表明风险/保护因素之间存在相互作用，但聚类分析确定了4种具有不同风险因素特征的亚型。在第1组中，所有患者都有PD家族史，而30%的患者存在消化不良或接触有毒物质的情况。在第2组和第3组中，没有PD家族史，而接触有毒物质（第2组）和消化不良（第3组）起主要作用。第4组由没有风险因素的患者组成。
本研究表明，9个因素通过在同一患者中共存而非相互作用来独立改变PD风险。我们的研究表明，未来需要制定预防策略，旨在减少同一参与者体内不同风险因素的共存。
