Diet, Metabolomics, and Parkinson's Disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease that affects motor control and is characterized by several hallmark symptoms, including resting tremor, bradykinesia, rigidity, and postural instability. Existing treatments are unable to stop or slow the progression of PD. The lack of effective treatment is likely due in part to the fact that PD develops insidiously over an extended period such that there is already extensive and irreversible neurodegeneration by the time of clinical diagnosis. In order to deliver treatment before neurodegeneration is too extensive, it is therefore vital to better understand and reliably recognize the prodromal phase of PD. In Chapter 1, we used blood samples from 349 matched case-control pairs in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) to examine whether metabolites known to be associated with insulin resistance and diabetes were also associated with the development of PD. In these analyses, there was no evidence that these markers of insulin resistance and diabetes were associated with PD, corroborating previous research in these cohorts that failed to identify a relationship between diabetes and PD. In Chapter 2, we used blood samples from 817 matched case-control pairs in the NHS, the HPFS, and the Cancer Prevention Study II Nutrition Survey Cohort (CPS-IIN) to investigate whether pre-diagnostic plasma metabolite levels could act as risk factors for or biomarkers of PD. Several metabolites were nominally associated with PD but, after adjustment for multiple testing, none remained significant. Further, we were unable to reliably distinguish cases from controls based on their metabolomic profiles. These results contradict several retrospective metabolomics investigations of PD and emphasize the need for careful study design in investigations of potential biomarkers. In Chapter 3, we assessed whether adherence to a Mediterranean-style diet was associated with non-motor features of prodromal PD. Here, we found that increased adherence to a Mediterranean-style diet was associated with a lower combined number of prodromal Parkinson’s features as well as with three specific features. These findings add further weight to the evidence that adherence to a Mediterranean-style diet could reduce the occurrence of specific features of prodromal Parkinson’s disease.