Increased Free Water in the Substantia Nigra in Asymptomatic LRRK2 G2019S Mutation Carriers

Background: The alteration of substantia nigra (SN) degeneration in populations at risk of Parkinson's disease (PD) is unclear. Objective: We investigated free water (FW) values in the posterior SN (pSN) in asymptomatic LRRK2 G2019S mutation carriers. Methods: We analyzed diffusion imaging data from 28 asymptomatic LRRK2 G2019S mutation carriers and 30 healthy controls (HCs), whereas 11 asymptomatic LRRK2 G2019S carriers and 11 HCs were followed up. FW values in the pSN were measured and compared between the groups. The relationship between longitudinal changes in FW in the pSN and dopamine transporter striatal binding ratio (SBR) was analyzed. Results: FW values in the pSN were significantly elevated and kept increasing during follow-up in asymptomatic LRRK2 G2019S carriers. There was a negative correlation between FW changes in the left pSN and SBR changes in the left putamen. Conclusion: FW in the pSN has the potential to be a progression imaging marker of early dopaminergic degeneration in the population at risk of PD. (c) 2022 International Parkinson and Movement Disorder Society.