Metabolic network abnormalities in drug-naive Parkinson's disease

Background: An ideal imaging biomarker for a neurodegenerative disorder should be able to measure abnormalities in the earliest stages of the disease. Objective: We investigated metabolic network changes in two independent cohorts of drugnaïve Parkinson's disease (PD) patients who have not been exposed to dopaminergic medication. Methods: We scanned 85 de novo, drug-naïve PD (dPD) patients and 85 age-matched healthy control subjects from Italy (n=96) and the United States (US, n=74) with [18F]- fluorodeoxyglucose (FDG) PET. All patients had clinical follow-ups to verify the diagnosis of idiopathic PD. Spatial covariance analysis was used to identify and validate de novo PD-related metabolic patterns (dPDRPs) in the Italian and US cohorts. We compared the dPDRPs to the original PDRP that was identified in more advanced patients who had been on chronic dopaminergic treatment. Results: De novo PD-related metabolic patterns, dPDRPs, were identified in each of the two independent cohorts of drug-naïve PD patients, and each differentiated PD patients from healthy control subjects. Expression values for these disease patterns were elevated in dPD patients relative to healthy controls in the identification as well as in each of the validation subgroups. The two dPDRPs were topographically very similar to each other and to the original PDRP. Conclusions: Reproducible PDRP patterns are expressed in de novo, drug-naïve PD patients. In PD, disease-related metabolic patterns have stereotyped topographies that develop independently of chronic levodopa treatment.