Genes, Environment, and Prodromal Features of Parkinson s Disease
Abstract
Parkinson s disease is the second most common neurodegenerative disease in the United States (U.S.) and affects over one million Americans; this number is growing due to population aging. Current treatments do not prevent disease progression, which ultimately results in severe disability. There is thus a compelling need to develop more effective treatments. The pathological process that leads to Parkinson s disease develops insidiously over more than ten years, and by the time the disease is recognized and treatment started, there is already extensive and irreparable brain loss. The consensus among experts is that an enormous advantage could be achieved by recognizing Parkinson s disease earlier in the disease process, before there is a substantial loss of brain cells. Our group has been working for several years to achieve this goal. We have been following over 150,000 men and women for decades who are participating in two large cohort studies, the Nurses Health Study, comprising over 100,000 women 30 to 55 years of age, and the Health Professionals Follow-Up Study, comprising over 50,000 men 40 to 65 years of age. These individuals have been followed with minimal losses for over 30 years, and are still actively participating in our investigations. Most importantly, both men and women have provided every 2-4 years comprehensive, validated, and updated information on their lifestyle, diet, family history, use of medications, and a detailed medical history; over one-third of participants has also provided blood samples for research purposes. Among the environmental exposures that have been assessed are air pollution (using geocoding for the area of residence) and pesticides (men only). The comprehensive, rigorous, and extensively validated information collected among participants in these cohorts has provided one of the major sources of our knowledge and scientific publications on risk factors for cancer, cardiovascular disease, and other conditions, including Parkinson s disease. In 2012, we have started screening several thousands of participants in these cohorts for features suggestive of early, still undiagnosed Parkinson s disease, and we have provided preliminary evidence that the combination of several of these features may be used to identify those individuals who are still in a preclinical phase. As part of this proposal, we plan to use DNA previously collected from these individuals to determine their genetic risk, and to integrate the genetic information with the data on risk factors and non-genetic characteristics to improve our ability to distinguish individuals with Parkinson s disease from those without. We expect that stratification by genetic factors will be important, because several of the characteristics that suggest the presence of early Parkinson s disease, such as intestinal constipation, are due to a variety of causes and are commonly observed in individuals without the disease. The proposed research will be helpful for all individuals at risk of developing Parkinson s disease. The observation in clinical and epidemiological studies that physical activity and some dietary factors may contribute to the prevention of PD, suggests that these factors may also delay the disease progression in individuals who are in the preclinical phase of the disease. Trials of physical activity and several drugs that are expected to slow the disease progression are ongoing, but they are being conducted among patients who already have clinical disease and thus, substantial brain damage, when it may be too late to achieve the best possible results. Relatively harmless interventions, such as increases in physical activity or dietary changes, could be implemented in individuals with moderate to high probability of having prodromal PD, in which the benefits, even if uncertain, are likely to offset the risks. On the other hand, the testing of novel drugs will require a high degree of diagnostic accuracy, which could be ach
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010303
Entities
People
- Alberto Ascherio
Organizations
- President and Fellows of Harvard College
- United States Army