Objective: To assess whether any of the biomarkers studied (UPDRS-III, SN echogenicity, UPSIT and DaT-SPECT) in a baseline evaluation of a cohort of LRRK2 G2019S asymptomatic carriers was helpful to predict conversion to PD in a 4-year period. To estimate through sequential DaT-SPECT imaging the rate of progression of the dopaminergic terminal loss in the premotor stage of the disease.

Background: The G2019S mutation of LRRK2 is the commonest known cause of Parkinson’s disease (PD). The follow-up of asymptomatic carriers of this mutation represents a unique opportunity for studying the prodromal stage of PD. Besides age no other clinical marker is useful to predict conversion to PD in asymptomatic carriers. In a previous study we characterized with brain imaging and olfaction tests a cohort of 32 asymptomatic carriers of LRRK2 G2019S mutation

Methods: Thirty-two asymptomatic carriers of LRRK2 G2019S mutation with baseline and 4-year evaluation including clinical examination (UPDRS-III and olfaction UPSIT test) and 123I-ioflupane SPECT. Visual and semiquantitative analysis of images was performed. The specific striatal binding ratio was calculated = Striatal ROI-Occipital ROI/Occipital ROI.

Results: Three carriers, asymptomatic at baseline, had converted to PD at the 4-year evaluation. Age and UPDRS-III at baseline was higher, although not significantly, in PD converters. Mean UPSIT score at baseline was not different between PD-converters and non-converters and the same at 4-year after adjusting for age (21.3 ± 4.5 vs 29.2 ± 3.5; p-adjusted= 0.23). The mean reduction in the ratio of mean bilateral striatum 123I-ioflupane uptake was 0.33 ± 1.6, with no differences between PD-converters and non-converters. The slope of the decline in DaT binding was similar between both groups, however PD-converters has significantly lower 123I-FP-CIT uptake at baseline than non-converters (p= 0.002). A baseline scan with a ratio of bilateral striatal uptake below 1 predicted with 100% sensitivity and specificity conversion to PD within the four-year period (AUC= 1, p = 0.006).

Conclusions: Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of LRRK2 G2019S mutation. Rate of conversion to PD at 4 years in this cohort aged ~ 64 years was 12%. The slope of DaT binding decline was similar across different premotor stages of the disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progression-to-parkinsons-disease-in-carriers-of-lrrk2-g2019s-mutation-a-4-year-prospective-study-with-serial-dopamine-transporter-imaging/