INTRODUCTION:The majority of Parkinson's disease (PD) patients undergoing treatment with levodopa (LD) -the first-line therapy for motor manifestations in PD- experience OFF episodes, characterized by symptom exacerbation. Inhaled LD is an on-demand therapy aimed at managing OFF episodes. METHODS:A scientific committee comprising six PD experts developed statements regarding inhaled LD based on evidence and their clinical practice experience. Using a two-round Delphi study, these statements were evaluated on a Likert scale ranging from 1 (completely disagree) to 9 (completely agree) by a panel of Spanish neurologists specialising in the management of PD patients. Consensus was considered achieved if ≥ 66.67% of responses fell within the same tertile as the median response for each statement ([1-3] disagreement, [4-6] neutral, [7-9] agreement). RESULTS:Forty-four statements across six thematic areas were developed. A total of 48 experts were invited to participate in the Delphi study, with participation rates of 91.7% in the first round and 83.3% in the second. After two rounds, consensus was reached in agreement on 40 out of 44 statements (91%). There was a high degree of expert consensus on the utility of inhaled LD for the rapid and reliable on-demand treatment of both motor and non-motor fluctuations in PD patients. CONCLUSIONS:Inhaled LD was deemed a useful, effective, and safe on-demand treatment for OFF episodes in PD.

Introducción La mayoría de los pacientes con enfermedad de Parkinson (EP) en tratamiento con levodopa (LD) —el tratamiento de primera línea para manifestaciones motoras en EP— experimenta episodios OFF, con exacerbación de síntomas. La LD inhalada es una terapia a demanda para manejar los episodios OFF. Métodos Un comité científico compuesto por 6 expertos en EP desarrollaon sentencias sobre LD inhalada, basadas en la evidencia y su experiencia en la práctica clínica. Con un estudio Delphi de 2 rondas, las sentencias fueron evaluadas en una escala Likert de 1 (completamente en desacuerdo) a 9 (completamente de acuerdo) por un panel de neurólogos españoles expertos en el manejo de los pacientes con EP. Se consideró que se alcanzó el consenso si ≥66,67% de las respuestas se situaban en el mismo tercil que la mediana de las respuestas para cada sentencia ([1-3] desacuerdo, [4-6] indeterminado, [7-9] de acuerdo). Resultados Se desarrollaron 44 sentencias en 6 áreas temáticas. Se invitó a participar en el estudio Delphi a 48 expertos, y la tasa de participación fue del 91,7% en la primera ronda y 83,3% en la segunda. Tras las 2 rondas, se alcanzó consenso en el acuerdo en 40 de las 44 sentencias (91%). Hubo un alto grado de consenso entre expertos en la utilidad de la LD inhalada para tratar a demanda, de manera rápida y fiable, fluctuaciones motoras y no motoras en los pacientes con EP. Conclusiones La LD inhalada fue considerada como un tratamiento a demanda útil, eficaz, y seguro para los episodios OFF en EP.

Dysphagia at time of diagnosis suggests atypical parkinsonism instead Parkinson´s disease (PD). Our aim was to analyze the frequency of dysphagia in patients with early PD comparing with a control group and to identify related factors. Patients with early PD (≤ 2 years from symptoms onset) who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated annually for 5 years from the Spanish cohort COPPADIS were included in this prospective study. Controls were assessed at baseline and at 2-, 4-, and 5-year follow-up. Dysphagia was defined as a score ≥ 1 in the item 20 of the Non-Motor Symptoms Scale (NMSS). Dysphagia was more frequent at baseline in PD patients (19.6

Parkinson’s Disease (PD)-associated subjective cognitive decline (PDSCD) is defined as cognitive complaints without objective cognitive impairment. Based on most studies, it is associated with a greater risk of cognitive decline and may represent a prodromal stage of cognitive impairment. The main objectives are to identify cognitive progression patterns and clinical predictors of worse cognitive decline within a large PD-SCD cohort with a 4-year followup. All patients belong to the prospective observational multicenter study COPPADIS. A total of 198 PD-SCD subjects were analyzed. Mean age was 60.9, mean disease duration 5.2, and mean PD-Cognitive Rating Scale (PD-CRS) 97.6. Subjects were classified as Progressors if their Reliable Change Index was ≤ − 1.64 at year 4, and as non-Progressors if it was > − 1.64 (− 1.64 corresponded to − 16 on the PD-CRS). Progressors had significantly higher age, Movement Disorders Society-Unified PD Rating Scale (MDS-UPDRS) III, levodopa equivalent daily-dose, Non-Motor Symptom Scale total score, memory-related cognitive complaints, and prevalence of REM-sleep behavior disorder (RBD) at baseline. A linear mixed-effects model showed divergent cognitive trajectories between Progressors and non-Progressors (estimate = − 26.8; p < 0.001), with no differences in motor trajectories. In the binary regression model, age (OR = 1.09; p = 0.001), MDS-UPDRS III (OR = 1.05, p = 0.008), and RBD (OR = 2.55, p = 0.010) at baseline were independent predictors of cognitive progression. Subjects with PD-SCD do not consistently show cognitive decline, but rather exhibit a heterogeneous progression. Age, MDS-UPDRS III and RBD significantly increase the risk of a more aggressive cognitive phenotype. Future research on biomarkers will help explore additional cognitive predictors in PD-SCD.

Background and objective: Level of Education (LoE) is widely used as an indicator of cognitive reserve and is associated with risk of dementia. The aim of the present study was to know the influence of the LoE on the change in cognitive function (CF) in patients with Parkinson´s disease (PD). Patients and Methods: Controls and PD patients from the Spanish cohort COPPADIS with a disease duration from symptoms onset ≤ 5 years, who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated at 2 (V2), 4 (V4) and 5 (V5) years of follow-up were included. Regarding LoE, patients were classified as with primary, secondary and university studies. CF was assessed using the Parkinson´s Disease Cognitive Rating Scale (PD-CRS). General linear model (GLM) repeated measure was used to test for changes in the CF. Results Three hundred and ninety-nine PD patients (61.9 ± 8.9 years old; 58.4% males) and 207 controls (61 ± 8.3 years old; 49.8% males) were included. From V0 to V5, significant differences were observed in PD patients in global and fronto-subcortical (p < 0.0001 in all visits) between LoE groups but not in posterior-cortical (p > 0.05 in all visits) CF. LoE was associated with the change from V0 to V5 in the PD-CRS total score and fronto-subcortical sub-score (p < 0.0001) in PD patients but not in controls. Having primary studies was associated to PD dementia (PD-CRS < 65) at V5 (OR = 2.47; p = 0.035). Conclusion Change in cognitive function in Parkinson´s disease is influenced by the level of education.

BACKGROUND AND PURPOSE:Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients. METHODS:A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected. RESULTS:Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG. CONCLUSIONS:LECIG was safe and effective in advanced PD patients.

Background and objective: Staging Parkinson’s disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients’ quality of life and caregivers’ strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT). Patients and Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study). The MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) were collected by the neurologist at V0 (before starting LECIG) and V2 (follow-up visit). Wilcoxon’s signed rank and Marginal Homogeneity tests were applied to compare changes from V0 to V2. Results: Sixty-seven PD patients (58.2% males; 69.9 ± 9.3 years old) with a mean disease duration of 14.4 ± 6.5 years were included. The mean treatment duration (V2) was 172.9 ± 105.2 days. At V0, patients were classified as in stage 2 (35.8%), 3 (46.3%) or 4 (17.9%). The frequency of patients in stage 4 decreased to 9% at V2 (p = 0.001). The MNCD total score decreased from 6.27 ± 1.94 at V0 to 5.21 ± 2.23 (p < 0.0001). From V0 to V2, the motor (M; p < 0.0001) and non-motor symptom (N; p < 0.0001) burden decreased, and autonomy for the activities of daily living (D; p = 0.005) improved. Conclusions: The MNCD classification could be useful to classify advanced PD patients and to monitor the response to a DAT.

ABSTRACTBackgroundLevodopa‐induced dyskinesias (LID) are frequent in Parkinson's disease (PD).ObjectiveTo analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients’ quality of life (QoL).Patients and MethodsPD patients from the 5‐year follow‐up COPPADIS cohort were included. LID were defined as a non‐zero score in the item “Time spent with dyskinesia” of the Unified Parkinson's Disease Rating Scale—part IV (UPDRS‐IV). The UPDRS‐IV was applied at baseline (V0) and annually for 5 years. The 39‐item Parkinson's disease Questionnaire Summary Index (PQ‐39SI) was used to asses QoL.ResultsThe frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5‐year follow‐up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (β = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (β = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ‐39SI.ConclusionLID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.