Metabolic Network Abnormalities in Drug-Naïve Parkinson's Disease

Mov Disord. 2020 Apr;35(4):587-594. doi: 10.1002/mds.27960. Epub 2019 Dec 24.

Abstract

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 [18 F]-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.

Keywords: PET; Parkinson's disease; drug naïve; imaging biomarker; network analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Italy
  • Levodopa
  • Metabolic Networks and Pathways
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / drug therapy
  • Pharmaceutical Preparations*

Substances

  • Pharmaceutical Preparations
  • Levodopa