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A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had

PROPAG-AGEING consortium., A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had, This project has received funding from the European Union’s Horizon 2020 research and innovation program Propag‐Ageing under grant agreement no. 634821.

Introduction: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. Methods: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. Results: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68% higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. Conclusion: These are the first observations on DAs pharmacokinetics in PD patients’ everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.

none 13 no Italian Ministry of Research RFO, Fondazione del Monte, Fondazione Gino Galletti to SC, PP, RL and AIRAlzh Onlus-COOP Italia to ABS. The C9orf72 repeat expansion (RE) is one of the most frequent causative mutations of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, it is still unclear how the C9orf72 RE can lead to a heterogeneous phenotype. Several reports have shown the coexistence of mutations in multiple ALS/FTD causative genes in the same family, suggesting an oligogenic etiology for ALS and FTD. Our aim was to investigate this phenomenon in an Italian group of ALS/FTD pedigrees carrying the C9orf72 RE. We included 11 subjects from 11 pedigrees with ALS/FTD and the C9orf72 RE. Mutation screening of FUS, SOD1 and TARDBP genes was performed by direct sequencing. A dementia-specific custom-designed targeted next-generation sequencing panel was used for screening dementia-associated genes mutations. We found genetic variants in additional ALS or dementia-related genes in four pedigrees, including the p.V47A variant in the TYROBP gene. As a group, double mutation carriers displayed a tendency toward a younger age at onset and a higher frequency of positive familiar history and of parkinsonism. Our observation supports the hypothesis that the co-presence of mutations in different genes may be relevant for the clinical expression of ALS/FTD and of their oligogenic nature. mixed Giannoccaro, Maria Pia; Bartoletti-Stella, Anna; Piras, Silvia; Pession, Annalisa; De Massis, Patrizia; Oppi, Federico; Stanzani-Maserati, Michelangelo; Pasini, Elena; Baiardi, Simone; Avoni, Patrizia; Parchi, Piero; Liguori, Rocco; Capellari, Sabina Giannoccaro, Maria Pia; Bartoletti-Stella, Anna; Piras, Silvia; Pession, Annalisa; De Massis, Patrizia; Oppi, Federico; Stanzani-Maserati, Michelangelo; Pasini, Elena; Baiardi, Simone; Avoni, Patrizia; Parchi, Piero; Liguori, Rocco; Capellari, Sabina

Background Advanced brain MR techniques are useful tools for differentiating Progressive Supranuclear Palsy from Parkinson's disease, although time-consuming and unlikely to be used all together in routine clinical work. We aimed to compare the diagnostic accuracy of quantitative morphometric, volumetric and DTI metrics for differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease. Methods 23 Progressive Supranuclear Palsy-Richardson's Syndrome and 42 Parkinson's disease patients underwent a standardized 1.5T brain MR protocol comprising high-resolution T1W1 and DTI sequences. Brainstem and cerebellar peduncles morphometry, automated volumetric analysis of brain deep gray matter and DTI metric analyses of specific brain structures were carried out. We determined diagnostic accuracy, sensitivity and specificity of MR-markers with respect to the clinical diagnosis by using univariate receiver operating characteristics curve analyses. Age-adjusted multivariate receiver operating characteristics analyses were then conducted including only MR-markers with a sensitivity and specificity exceeding 80%. Results Morphometric markers (midbrain area, pons to midbrain area ratio and MR Parkinsonism Index), DTI parameters (infratentorial structures) and volumetric analysis (thalamus, putamen and pallidus nuclei) presented moderate to high diagnostic accuracy in discriminating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, with midbrain area showing the highest diagnostic accuracy (99%) (mean ± standard deviation: 75.87 ± 16.95 mm2vs 132.45 ± 20.94 mm2, respectively; p, Highlights • We compared quantitative brain MR markers accuracy to differentiate advanced stages of PSP-RS from PD. • Quantitative morphometric, DTI and volumetric data showed moderate-high accuracies. • Midbrain area alone best discriminated advanced PSP-RS from PD (99%). • Midbrain area evaluation should be added to brain MR protocols for parkinsonisms.