An MRI Atrophy Biomarker Predicts Global Prognosis in Early De Novo Parkinson’s Disease

Abstract

Background: Commonly used neuroimaging biomarkers in Parkinson's disease (PD) are useful for diagnosis but poor at predicting outcomes. We explored whether an atrophy pattern from whole-brain structural MRI, measured in the drug-naïve early stage, could predict PD prognosis.Methods: 362 de novo PD patients with T1-weighted MRI (n=222 for the main analysis, 140 for the validation analysis) were recruited from the Parkinson's Progression Markers Initiative (PPMI). We investigated a previously identified PD-specific network atrophy pattern as a potential biomarker of disease severity and prognosis. Progression trajectories of motor function (MDS-UPDRS-part III), cognition (Montreal Cognitive Assessment (MoCA)), and a global composite outcome measure were compared between atrophy tertiles using mixed effect models. The prognostic value of the MRI atrophy measure was compared with 123 I ioflupane single photon emission computed tomography, the postural-instability-gait-disturbance score, and cerebrospinal fluid markers. Findings: After 4.5 years follow-up, PD-specific atrophy network score at baseline significantly predicted change in UPDRS-part III (r=-0.197, p=0.003), MoCA (r=0.253, p=0.0002) and global composite outcome (r=-0.249, p=0.0002). Compared with the 3 rd tertile (i.e. least atrophy), the tertile with the highest baseline atrophy (i.e. the 1st tertile) had a 3-point annual faster progression in UPDRS-part III (p=0.012), faster worsening of posture-instability gait scores (+0.21 further annual increase, p<0.0001), faster decline in MoCA (-0.74 further annual decline in MoCA, p =0.0372) and a +0.38 ( p =0.0029) faster annual increase in the global composite z-score. All findings were replicated in a validation analysis using 1.5T MRI. By comparison, the other biomarkers were limited in their ability to predict prognosis either in the main or validation analysis.Interpretation: A PD-specific network atrophy pattern predicts progression of motor, cognitive, and global outcome in PD, and is a stronger predictor of prognosis than any of the other tested biomarkers. Therefore, it has considerable potential as a prognostic biomarker for clinical trials of early PD. METHODS ParticipantsPD patients with age ≥30, a diagnosis of PD within the last 2 years, a baseline Hoehn and Yahr stage of I or II, and no anticipated need for symptomatic treatment within six months of entry were recruited by the Parkinson's Progression Markers Initiative (PPMI) (see:early idiopathic PD.6 Selection criteria included asymmetric resting tremor or asymmetric bradykinesia or two of bradykinesia, resting tremor and rigidity, plus confirmation of a dopaminergic deficit using dopamine transporter imaging (see below). For the current study, we also excluded any participant with less than one year of follow-up or no MRI available. Therefore, 362 de novo treatment-naive PD patients were included. Of these, 222had 3T MRI and 140 had 1.5T MRI.The relevant local institutional review boards approved the PPMI protocol and written informed consent wa...