Prospective studies on Parkinson's disease

点击翻译按钮获取中文摘要

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 for most PD cases remain unclear. Epidemiological studies on PD environmental risk factors are proven difficult, due to the low incidence, the insidious onset and the clinical course of the disease. I am currently conducting the Parkinson's Genes and Environment Study (PAGE) to investigate environmental and genetic risk factors for PD. We designed the PAGE study by taking advantage of the infrastructure of NIH-AARP Diet and Health Study, a large cancer cohort that was established by the National Cancer Institute about 10 years ago. At baseline, NCI collected detailed information on diet and lifestyle. In the PAGE study, we are confirming self-reported PD diagnoses and collecting genetic materials from PD cases and selected controls. To date, we have successfully recruited over 1,100 potential PD patients and 1,900 controls. Compared with previous PD epidemiological projects, the PAGE study is the largest with both DNAs and prospectively collected non-genetic exposures. There are two primarily goals of the PAGE study. The first is to examine prospectively diet and lifestyle risk factors for PD, by using exposure data collected at NIH-AARP DH baseline surveys and PD cases identified during the follow-up. Other than smoking and coffee drinking, no other environmental risk factors for PD have been established. Common limitations of the previous studies are small sample size and retrospectively collected exposure data. Therefore many of the previous PD findings are crude and controversial. With a large sample size and prospectively collected exposures in PAGE, we would be able to clarify previous PD findings and identify novel risk factors. The second primary aim is to investigate roles of genes and gene-environment interactions by analyzing genetic data from PD cases and controls. The large sample size and systematically collected exposure offer a good opportunity to investigate gene-environment interactions. In addition, my group is also working on a few other projects in collaboration with intra- and extramural investigators to search for causes of PD and other neurodegernerative diseases. These studies include the Health Professionals Follow-up Study, the Nurses Health Study, the Cancer Prevention Study II Nutrition Cohort, and the Arthrosclerosis Risk in Community Study. Finally, my group is planning for international collaboration on Parkinson research.