Category: Parkinson's Disease: Genetics
Objective: To characterize the 8-year progression of clinical and imaging biomarkers in a cohort of asymptomatic LRRK2 G2019S carriers and to assess its utility as predictors of PD phenoconversion.
Background: •The identification and follow-up of asymptomatic carriers of the LRRK2 G2019S mutation represents a unique opportunity for studying the prodromal stage of PD.We previously characterized with 123I-ioflupane SPECT and olfaction testing a cohort of 32 asymptomatic carriers of the LRRK2 G2019S mutation (Sierra M, Neurology 2013; Sierra M, Neurology 2017)
Method: Twenty-five asymptomatic carriers of LRRK2 G2019S mutation with baseline and 4-year evaluation, and 17 with 8-year evaluation including clinical examination (UPDRS-III, olfaction UPSIT test) and DaT-SPECT (123I-ioflupane). The specific striatal binding ratio was calculated as follows: Striatal binding ratio= Striatal ROI-Occipital ROI/Occipital ROI.A lineal mixed model was used for the analysis.
Results: Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. One additional carrier converted at 8-years. PD-converters had lower striatal DaT binding at baseline than non-converters (p= 0.002). DaT binding ratio declined significantly between baseline and 8-year evaluation, with a mean annual rate of 3.6%, with somewhat variability and comparable between PD-converters and non-converters. Older age and male sex were independently associated with DaT binding decline. No carrier with DAT binding ratio above an undefined threshold between 0.5 and 1 developed PD symptoms. Age-adjusted UPSIT score did not change significantly over the 8 years of follow-up.
Conclusion: Rate of conversion to PD at 8 years in this cohort aged ~ 58 years at baseline was 16%. The observed decline of DaT binding over time and its association with the phenotype turn DaT-SPECT into a potentially useful tool for monitoring the premotor stage of the disease. However, the intraindividual variability of the slope across the different periods makes it unfeasible to accurately predict the time of phenoconversion.
To cite this abstract in AMA style:A. Sánchez Rodríguez, I. Martínez Rodríguez, M. Sierra, P. Sánchez Juan, I. González Aramburu, M. Rivera Sánchez, J. Andrés Pacheco, A. Gutiérrez-González, O. Cuenca-Vera, J. Madera, A. García-Hernández, J. Infante. Serial DaT-SPECT imaging in asymptomatic carriers of LRRK2 G2019S mutation: 8-years follow-up [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/serial-dat-spect-imaging-in-asymptomatic-carriers-of-lrrk2-g2019s-mutation-8-years-follow-up/. Accessed November 29, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/serial-dat-spect-imaging-in-asymptomatic-carriers-of-lrrk2-g2019s-mutation-8-years-follow-up/