Substantia Nigra Neuromelanin Magnetic Resonance Imaging in LRRK2 Asymptomatic Carriers

Background: Neuromelanin (NM)-sensitive MRI of the substantia nigra is a biomarker of neurodegeneration in Parkinson's disease (PD), which is expected to begin years before motor symptoms emerge, and for which LRRK2 mutation asymptomatic carriers (AC) are at higher risk. Objectives: To investigate NM-MRI in asymptomatic LRRK2 carriers. Methods: Asymptomatic first-degree relatives of LRRK2-PD patients were sequentially recruited. An extensive clinical evaluation and a study of NM using a specific T1-weighted MRI sequence, were performed. Targeted genetic testing for LRRK2 variants was performed after evaluation. Results: Nineteen asymptomatic participants were included, 12 LRRK2-G2019S non-carriers (NC) and 7 AC. Demographics and motor scores, assessed using MDS-UPRS-III, did not differ between groups. NM area was smaller in AC when compared to NC (16 mm²[14.9–19.1] vs 20.6 mm²[19.3–24.0], P = 0.025). Conclusion: NM-MRI can be significantly decreased in LRRK2-G2019S AC. This technique may be a promising biomarker of neurodegeneration in pre-diagnostic stages of PD.