Abnormalities in Metabolic Network Activity Precede the Onset of Motor Symptoms in Parkinson's Disease

Abstract

Imaging studies show that Parkinson's disease (PD) alters the activity of motor- and cognition-related metabolic brain networks. However, it is not known whether the network changes appear at or before symptom onset. In this study, we examined 15 hemiparkinsonian patients who underwent serial metabolic imaging with [18F]-fluorodeoxyglucose (FDG) PET at baseline and again 2.1 ± 0.6 (mean ± SD) and 3.9 ± 0.7 years later. We assessed longitudinal changes in network activity in each cerebral hemisphere, focusing specifically on the “presymptomatic” hemisphere—ipsilateral to the initially involved body side. At the network level, the activity of the PD motor-related pattern (PDRP) increased symmetrically in both hemispheres over time (p< 0.001), with significant bilateral elevations at each of the three time points. Hemispheric expression of the PD cognition-related pattern likewise increased symmetrically (p< 0.001), although significant elevations were not evident on either side until 4 years. At the regional level, putamen metabolism contralateral to the initially affected body side was elevated at all three time points, without longitudinal change. In contrast, in the initially presymptomatic hemisphere, putamen metabolic activity increased steadily over time, reaching abnormal levels only at 4 years. Metabolic activity in the contralateral precuneus fell to subnormal levels by the final time point. These findings suggest that abnormal PDRP activity antecedes the appearance of motor signs by ∼2 years. The timing and laterality of symptom onset relates to focal asymmetric metabolic changes at the putamenal node of this network.