Prospective studies on Parkinson's disease

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Parkinson?s disease (PD) is the second most prevalent neurodegenerative disease in the elderly population and its causes are largely unknown. Although several genes have been identified to be responsible for some of the early onset familial cases, the causes of most PD cases remained unexplained. Epidemiological studies on PD environmental risk factors are proved difficult, due to the low incidence, the insidious onset and the clinical course of the disease. In collaboration with Dr. Alberto Ascherio?s group at Harvard School of Public Health, I have been investigating dietary and lifestyle risk factors in relation to PD risk in three well established prospective cohorts: the Health Professionals? Follow-up Study, the Nurses? Health Study, and the Cancer Prevention Study II Nutrition Cohort from American Cancer Society. The prospective design is important in PD epidemiological research as it avoids many of the potential biases that the previous case-control studies had. Further, these three cohrots are to date the largest prospective studies on PD and have generated some interesting results that need to be validated in future investigations. Consistent findings from these studies included a positive association between dairy consumption and risk of PD and an inverse association between non-aspirin NSAIDs use and PD risk. Recently, we were also able to provide to date the strongest prospective evidence linking pesticide use and a higher PD risk. Further, I am also developing a new research project on PD (the Parkinson?s Genes and Environment Study (PAGE)) to investigate environmental and genetic risk factors for PD in the NIH-AARP Diet and Health Study, which is a large prospective cohort that was initiated in mid-1990s by Dr. Arthur Schatzkin at NCI for cancer research. Over half a million US men and women 50 years or older participated in the baseline surveys in 1995 and 1996 and a follow-up survey is now underway to document the occurrence of chronic diseases, including PD. Therefore, this cohort provides an excellent infrastructure for PD research. The PAGE study includes two phases: PAGE 1 is a longitudinal study to investigate whether diet/lifestyle are related to PD risk, using exposure information collected at baseline and PD cases identified in the follow-up. PAGE 2 will be a case-control study to examine other environmental/occupational risk factors in relation to PD and will require further retrospective exposure data collection from both cases and selected controls. For both projects, the key is to do an accurate diagnostic confirmation of PD cases, and an intrinsic component of both projects is DNA collection, which will allow us to conduct case-control analyses of diet-gene / environment-gene interactions. Therefore, PD diagnostic confirmation and DNA collection will be carried out as part of PAGE 1. In PAGE2, we will conduct retrospective data collection using computer assisted telephone interview (CATI). Of particular interest are exposures to pesticides, heavy metals, medication, and history of infectious diseases. Eventually, we expect to confirm approximately 1,000 incident PD cases (1996-2004) based on the age- and gender-specific incidence from other large prospective cohorts with similar design. This will make the study the largest longitudinal study on PD to date and thus contribute significantly to our understanding of the environmental and genetic causes of late onset sporadic PD. We just started data collection for the PAGE study.