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Serial DaT-SPECT imaging in asymptomatic carriers of LRRK2 G2019S mutation: 8 years' follow-up

Abstract: Background: Carriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of Parkinson's disease (PD). We have studied by serial clinical and dopamine transporter single photon emission computed tomography (DaT-SPECT) evaluations a cohort of asymptomatic carriers of the 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. Methods: Seventeen participants, of the 25 available from the 4-year evaluation, completed the 8-year assessment. UPDRS-III, UPSIT test and DaT-SPECT imaging (123I-ioflupane) were performed. We used repeated-measures linear mixed effects models to examine the changes in DaT binding over time. Results: 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-individual and intra-individual 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. Conclusions: 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 render DaT-SPECT a potentially useful tool for monitoring the premotor stage of the disease, although at the individual level its ability to predict phenoconversion is limited.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: European journal of neurology, 2021;28:4204? 4208

Editorial: Wiley

 Fecha de publicación: 01/12/2021

Nº de páginas: 13

Tipo de publicación: Artículo de Revista

 DOI: 10.1111/ene.15070

ISSN: 1351-5101,1468-1331

Url de la publicación: https://doi.org/10.1111/ene.15070

Autoría

SÁNCHEZ- RODRÍGUEZ, ANTONIO

MARTÍNEZ-RODRÍGUEZ, ISABEL

SÁNCHEZ-JUAN, PASCUAL

SIERRA, MARÍA

GONZÁLEZ-ARAMBURU, ISABEL

RIVERA-SÁNCHEZ, MARÍA

ANDRÉS- PACHECO, JAVIER

GUTIERREZ-GONZÁLEZ, ÁNGELA

GARCÍA-HERNÁNDEZ, ADRIÁN

MADERA, JORGE

DELGADO-ALVARADO, MANUEL