Substantia Nigra Volume Loss Before Basal Forebrain Degeneration in Early Parkinson Disease

Objective: To test the hypothesis that degeneration of the substantia nigra pars compacta (SNc) precedes that of the cholinergic basal forebrain (BF) in Parkinson disease (PD) using new multispectral structural magnetic resonance (MR) imaging tools to measure the volumes of the SNc and BF. Design: Matched case-control study. Setting: The Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), and the Massachusetts General Hospital/MIT Morris Udall Center of Excellence in Parkinson Disease Research. Patients: Participants included 29 patients with PD (Hoehn and Yahr [H&Y] stages 1-3) and 27 matched healthy control subjects. Main Outcome Measures: We acquired multiecho T1-weighted, multiecho proton density, T2-weighted, and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences from each participant. For the SNc, we created a weighted mean of the multiple echoes, yielding a single volume with a high ratio of contrast to noise. We visualized the BF using T2-weighted FLAIR images. For each participant, we manually labeled the 2 structures and calculated their volumes. Results: Relative to the controls, 13 patients with H&Y stage 1 PD had significantly decreased SNc volumes. Sixteen patients with H&Y stage 2 or 3 PD showed little additional volume loss. In contrast, the BF volume loss occurred later in the disease, with a significant decrease apparent in patients having H&Y stage 2 or 3 PD compared with the controls and the patients having H&Y stage 1 PD. The latter group did not differ significantly from the controls. Conclusion: Our results support the proposed neuropathological trajectory in PD and establish novel multispectral methods as MR imaging biomarkers for tracking the degeneration of the SNc and BF. JAMA Neurol. 2013;70(2):241-247. Published online November 26, 2012. doi:10.1001/jamaneurol.2013.597-