Parkinson's disease (PD) is a multi-factorial neurodegenerative disorder whose pathogenesis depends on a combination of genetic and environmental factors. PD is characterized by wide variability in the presentation and progression that is possibly linked to the contribution of different risk factors. In the current literature, however, there are no conclusive findings on the relationship between most of the risk factors investigated and PD. We performed a systematic database search and we identified 62 risk factors that may either trigger or prevent the development of PD. The aim of the present multicenter case-control study will be to simultaneously evaluate the effects of the 62 risk factors on disease development, clinical variability and progression of PD. For this purpose, we will enrol 1000 patients affected by PD and 1000 age- and sex-matched healthy controls. The presence of the 62 risk factors will be investigated by the administration of a semi-structured questionnaire specifically developed according to the results of our database search. We will collect the PD patients' demographic and clinical data. The clinical assessment will be performed at the baseline and after a 1-year follow-up period. To identify independent risk and protective factors for PD development, we will compute a multivariate logistic regression analysis by using the demographic and risk factors data of our population. To identify PD clinical subtypes, we will use the demographic and clinical variables to perform `data-driven' cluster analysis. Finally, by performing the 1 year- follow up assessment we will investigate the possible effects of the 62 risk factors examined on PD progression. The present study will allow to clarify the independent influence of 62 risk/protective factors on PD development and progression and to ascertain whether the existence of different clinical subtypes in PD may also depend on the contribution of different risk factors.
The cause of Parkinson's disease (PD) is multi factorial, and both genetic and environmental factors contribute to the disease risk. Numerous studies assessing environmental risk factors possibly associated with PD have been published but several caveats cast doubts on their validity. Therefore, the environmental contribution to PD is still largely uncertain and there are at present no well-established risk factors to assist disease prevention. The simultaneous assessment of a wide spectrum of potential risk factors for PD development and progression in a large population of PD patients is the key point of our proposal. This will allow us a better understanding of the complex interplay among possible risk factors for PD development and progression, the identification of risk factors that are independently associated with PD (without evidence of confounding bias) and a comprehensive comparison of risk factors strength. Moreover, identification of environmental factors affecting the rate of PD progression might be relevant to the development of a strategy filling one of the current major gaps in the management of PD, the lack of disease-modifying treatment. Our study will also aid a better understanding of the mechanisms underlying PD clinical subtypes. This is one of the top three clinical research priorities in Parkinson's disease established in 2014 by the National Institutes of Health (NIH). By investigating the possible association between PD clinical subtypes and environmental risk factors, our proposal will clarify whether the clinical subtypes reflect the presence of different environmental risk factors and neurophysiological mechanisms.
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