Metabolic Network Abnormalities in Drug‐Naïve 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 drug‐naïve Parkinson's disease (PD) patients who have not been exposed to dopaminergic medication. Methods We scanned 85 de novo, drug‐naïve PD patients and 85 age‐matched healthy control subjects from Italy (n = 96) and the United States (n = 74) with [18F]‐fluorodeoxyglucose 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 in the Italian and U.S. cohorts. We compared the de novo PD‐related metabolic patterns to the original PD‐related pattern that was identified in more advanced patients who had been on chronic dopaminergic treatment. Results De novo PD‐related metabolic patterns 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 drug‐naïve PD patients relative to healthy controls in the identification as well as in each of the validation subgroups. The two de novo PD‐related metabolic patterns were topographically very similar to each other and to the original PD‐related pattern. Conclusions Reproducible PD‐related 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. © 2019 International Parkinson and Movement Disorder Society