María Sierra1, Isabel Martínez-Rodríguez1, Pascual Sánchez-Juan1, Isabel González-Aramburu1, Mikel Jiménez-Alonso1, Antonio Sánchez-Rodríguez1, José Berciano1, Ignacio Banzo1, Jon Infante2. 1. From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain. 2. From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain. jinfante@humv.es.
Abstract
OBJECTIVE: To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomatic LRRK2 G2019S carriers for predicting conversion to Parkinson disease (PD) at 4 years. METHODS: Thirty-two asymptomatic carriers of LRRK2 G2019S mutation underwent baseline and 4-year evaluation including clinical examination (Unified Parkinson's Disease Rating Scale, part III, olfaction University of Pennsylvania Smell Identification Test [UPSIT]) and dopamine transporter (DaT) SPECT (123I-ioflupane). Visual and semiquantitative analysis of images was performed. The specific striatal binding ratio was calculated (striatal region of interest [ROI] - occipital ROI/occipital ROI). RESULTS: Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (p = 0.002). A baseline scan with a ratio of bilateral striatal uptake below 1 predicted conversion to PD within the 4-year period with high sensitivity and specificity (area under the curve 1; p = 0.006). The slope of DaT binding decline between the 2 scans was similar in PD converters and nonconverters. Age-adjusted UPSIT score at baseline and at 4 years was similar in both groups. CONCLUSIONS: Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the 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 on DaT-SPECT imaging seems to be similar across different stages of the premotor period.
OBJECTIVE: To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomatic LRRK2G2019S carriers for predicting conversion to Parkinson disease (PD) at 4 years. METHODS: Thirty-two asymptomatic carriers of LRRK2G2019S mutation underwent baseline and 4-year evaluation including clinical examination (Unified Parkinson's Disease Rating Scale, part III, olfaction University of Pennsylvania Smell Identification Test [UPSIT]) and dopamine transporter (DaT) SPECT (123I-ioflupane). Visual and semiquantitative analysis of images was performed. The specific striatal binding ratio was calculated (striatal region of interest [ROI] - occipital ROI/occipital ROI). RESULTS: Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (p = 0.002). A baseline scan with a ratio of bilateral striatal uptake below 1 predicted conversion to PD within the 4-year period with high sensitivity and specificity (area under the curve 1; p = 0.006). The slope of DaT binding decline between the 2 scans was similar in PD converters and nonconverters. Age-adjusted UPSIT score at baseline and at 4 years was similar in both groups. CONCLUSIONS: Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the LRRK2G2019S mutation. Rate of conversion to PD at 4 years in this cohort aged ∼64 years was 12%. The slope of DaT binding decline on DaT-SPECT imaging seems to be similar across different stages of the premotor period.
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