Inés Legarda

Background and Objective: Sex differences in the treatment of people with Parkinson’s disease (PwP) with a device-aided therapy (DAT) have been poorly investigated. Our aim was to analyze sex differences in the management and response to a DAT in PwP in daily clinical practice (DCP). Patients and Methods: Data collected in the DATs-PD GETM Spanish Registry until 30 October 2025 were used. This is a descriptive, observational, prospective, and multicenter clinical registry with progressive inclusion of PwP treated with a DAT in DCP conditions in more than 40 centers from Spain. Sex differences in the DAT received and changes in quality of life (QoL), motor symptoms (MS), non-motor symptoms (NMS), and autonomy for activities of daily living (AADL) after 6 months of treatment were analyzed. Results: A total of 618 PD patients (66.9 ± 9.5 years old; 57.6% men) were treated with a DAT. A significant difference was observed in the DAT type according to sex (p = 0.006), with 73.1% of PwP who were treated with deep brain stimulation being men. At the time of DAT indication, women were older, received a higher levodopa equivalent daily dose, and had a worse health-related QoL and AADL. OFF time decreased, whereas MS and NMS burden and health-related QoL improved at 6 months follow-up in both groups (men and women). AADL improved only in men during the OFF state. Conclusion: Sex differences were detected in the use of DATs in PwP. Improvement in OFF time, MS, NMS, and QoL was detected in both groups.

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, “Off” time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD.

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson's disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to November 30, 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only 1 dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. Daily OFF time was reduced from Vpre to Vpost in 2.9 ± 1.9 hours (p=0.002). Conclusion: PwP improved significantly from Vpre to Vpost in motor symptoms (p=0.013), whereas a trend of significance was found for non-motor symptoms burden and quality of life. LECIG could be a good therapeutic option in PwP who failed fLD/fCD.

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.

Background and objective: Sex plays a role in Parkinson’s disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. Patients and Methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. Results: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001). Conclusion: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.

Background and objective: Parkinson’s disease (PD) is a clinically heterogeneous disorder in which the symptoms and prognosis can be very different among patients. We propose a new simple classification to identify key symptoms and staging in PD. Patients and Methods: Sixteen movement disorders specialists from Spain participated in this project. The classification was consensually approved after a discussion and review process from June to October 2021. The TNM classification and the National Institutes of Health Stroke Scale (NIHSS) were considered as models in the design. Results: The classification was named MNCD and included 4 major axes: (1) motor symptoms; (2) non-motor symptoms; (3) cognition; (4) dependency for activities of daily living (ADL). Motor axis included 4 sub-axes: (1) motor fluctuations; (2) dyskinesia; (3) axial symptoms; (4) tremor. Four other sub-axes were included in the non-motor axis: (1) neuropsychiatric symptoms; (2) autonomic dysfunction; (3) sleep disturbances and fatigue; (4) pain and sensory disorders. According to the MNCD, 5 stages were considered, from stage 1 (no disabling motor or non-motor symptoms with normal cognition and independency for ADL) to 5 (dementia and dependency for basic ADL). Conclusions: A new simple classification of PD is proposed. The MNCD classification includes 4 major axes and 5 stages to identify key symptoms and monitor the evolution of the disease in patients with PD. It is necessary to apply this proof of concept in a properly designed study.

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R² = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Background and objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.