ABSTRACT Parkinson's disease (PD), the most common neurodegenerative movement disorder, affects an estimated six million people worldwide and costs over $23 billion annually in healthcare costs in the US alone. A major portion of this cost is a direct result of the morbidity related to cognitive impairment that develops in 50-80% of PD patients. This morbidity appears to be driven by pathologic accumulation of the protein alpha-synuclein and Alzheimer disease (AD)-related pathologies. The ability to predict the development of cognitive impairment would have impact on prognosis, treatment, and clinical trial design for preventative therapies in PD. The goal of this project is to identify novel metabolomic markers associated with cognitive impairment in PD. This project will utilize gas chromatography mass-spectroscopy (GC-MS) and liquid chromatography- mass spectroscopy (LC-MS) methods to assess the blood- and cerebrospinal fluid-derived metabolome from advanced PD patients without cognitive impairment. We will then assess steady-state metabolomic profiles of plasma taken from patients before and after conversion to cognitive impairment which have been banked over time by the UK-Alzheimer's Disease Research Center, a portion of which have neuropathological correlation. The results of these studies will guide a more targeted approach to plasma biomarker evaluation before and after the conversion from normal to impaired cognition in patients drawn from the clinic population. The resources of the CNS-Met Metabolomics Core will be essential to the completion of these aims via assessment of steady-state metabolomics utilizing GC-MS and LC-MS. These studies are expected to provide new biomarker candidates for predicting conversion to cognitive impairment in PD and data for future R01-level applications.