Carriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of PD. We have studied by serial clinical and DaT-SPECT evaluations a cohort of asymptomatic carriers of LRRK2-G2019S mutation in order to evaluate the usefulness of these tools as biomarkers. Here we report the results of the extended follow-up of this cohort at 8 years.
Seventeen participants, out of 25 available from the 4-year evaluation, completed the 8-year assessment. UPDRS-III, UPSIT test and DaT-SPECT imaging ( I-ioflupane) was performed. We used repeated-measures linear mixed effects models to examine the changes in DaT binding over time.
Three carriers had converted to PD at 4-years. One additional carrier converted at 8-years. PD-converters had lower striatal DaT binding at baseline than non-converters. There was a significant decline of DaT binding over time, with a mean annual rate of 3.5%, with somewhat inter and intraindividual variability and comparable between PD-converters and non-converters. No carrier with DAT binding ratio above an undefined threshold between 0.5 and 0.8 developed PD symptoms. The age-adjusted UPSIT score did not change significantly over time.
The 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, although at the individual level its ability to predict phenoconversion is limited.

This article is protected by copyright. All rights reserved.

Author