Iria Cabo López

Background/Objectives: OFF episodes in Parkinson’s disease (PD) include motor and non-motor manifestations, but their resolution after on-demand therapy may not be synchronous. We examined within-patient temporal dynamics of motor and non-motor responses after inhaled levodopa. Methods: This post hoc analysis used data from the prospective, multicenter, open-label INLEVO-LIFE PD study. At week 12, UPDRS-III and 10 OFF-related non-motor symptoms (NMSs) were assessed in OFF and 30, 60, and 90 min after inhaled levodopa. The principal post hoc outcome was the proportion of maximum early (30–60 min) benefit retained at 90 min for motor versus non-motor outcomes. Individual trajectories were also examined descriptively. Results: Thirty-four participants had complete serial assessments. Mean UPDRS-III scores were 25.91, 11.21, 12.00, and 16.00 at OFF, 30, 60, and 90 min, respectively (p < 0.0001); corresponding NMSS-OFF/ON total scores were 6.65, 2.09, 1.91, and 2.71 (p < 0.0001). Among 28 participants with early improvement in both outcomes, median benefit retained at 90 min was 67.1% for motor symptoms versus 100% for NMSs (p = 0.0011). Motor and non-motor improvement magnitudes were not significantly correlated at any time point. Individual trajectories showed marked interindividual heterogeneity in the timing and persistence of motor and non-motor responses. Conclusions: Motor and non-motor OFF manifestations improved rapidly after inhaled levodopa but showed partially dissociated temporal trajectories, challenging the assumption that OFF resolution is necessarily synchronous across symptom dimensions. Greater relative persistence of non-motor benefit at 90 min is hypothesis-generating and requires confirmation using validated NMF instruments and controlled designs.

Background/Objectives: OFF episodes in Parkinson’s disease (PD) include motor and non-motor manifestations, but their resolution after on-demand therapy may not be synchronous. We examined within-patient temporal dynamics of motor and non-motor responses after inhaled levodopa. Methods: This post hoc analysis used data from the prospective, multicenter, open-label INLEVO-LIFE PD study. At week 12, UPDRS-III and 10 OFF-related non-motor symptoms (NMS) were assessed in OFF and 30, 60, and 90 min after inhaled levodopa. The principal post hoc outcome was the proportion of maximum early (30–60 min) benefit retained at 90 min for motor versus non-motor outcomes. Individual trajectories were also examined descriptively. Results: Thirty-four participants had complete serial assessments. Mean UPDRS-III scores were 25.91, 11.21, 12.00, and 16.00 at OFF, 30, 60, and 90 min, respectively (p < 0.0001); corresponding NMSS-OFF/ON total scores were 6.65, 2.09, 1.91, and 2.71 (p < 0.0001). Among 27 participants with early improvement in both outcomes, median benefit retained at 90 min was 61.9% for motor symptoms versus 100% for NMS (p = 0.0015). Motor and non-motor improvement magnitudes were not significantly correlated at any time point. Individual trajectories showed marked interindividual heterogeneity in the timing and persistence of motor and non-motor responses. Conclusions: Motor and non-motor OFF manifestations improved rapidly after inhaled levodopa but showed partially dissociated temporal trajectories, challenging the assumption that OFF resolution is necessarily synchronous across symptom dimensions. Greater relative persistence of non-motor benefit at 90 min is hypothesis-generating and requires confirmation using validated NMF instruments and controlled designs.

Background: CVT‐301 (Inbrija) has demonstrated its effectiveness in treating OFF periods in people with Parkinson's disease (PwP). However, its effect on non‐motor symptoms (NMS) and quality of life has not been researched yet. Our aim was to analyze the change observed in health‐related quality of life (HRQoL) and, as a secondary exploratory analysis, NMS associated with OFF episodes in PwP treated with CVT‐301. Methods: INLEVO‐LIFE PD (an open‐label study of the effect of INhaled LEVOdopa on quality of LIFE and non‐motor symptoms in Parkinson's Disease) is a prospective open‐label study conducted in five centers in Spain. The change from baseline (V0) to the end of the observational period (12 ± 2 weeks) (V12w) in the 39‐item Parkinson's Disease Quality of Life Questionnaire (PDQ‐39) total score was the primary efficacy measure. Results: Forty PD patients (age 62.3 ± 9.2 years; 55% males) were included between March/2024 and November/2025. At 12 weeks, 34 patients were using CVT‐301 and completed the follow‐up (85%). The PDQ39 total score decreased from 43.6 ± 24.2 at V0 to 31.4 ± 20.6 at V12w ( p < 0.0001). A significant decrease was observed in the mean score of 4 domains of the PDQ39. NMS burden was reduced at v12w from the OFF state to 30, 60, and 90 min after using CVT‐301 ( p < 0.0001). Mean daily OFF time decreased by 1.6 ± 1.9 h ( p < 0.0001). Adverse events related to CVT‐301 were reported in 35% of the patients. Conclusion: HRQoL and NMS associated with OFF episodes improved in PwP after 12 weeks using CVT‐301.

Background and Objective: Depression is frequent in Parkinson’s disease (PD), but it is unclear how mood changes and impacts patient’s quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) over 5 years of follow-up, comparing it with a control group, as well as its relationship with the patients’ QoL. Patients and Methods: PwP and healthy controls (HC) recruited from the COPPADIS cohort from January/2016 to November/2017 were included in this 5-year follow-up study. Mood was assessed by the Beck Depression Inventory II (BDI-II), and participants were classified as having major depression, minor depression, subthreshold depression, or non-depression at baseline and at 2, 4, and 5 years of follow-up. Correlation analysis and linear regression models were applied. Results: The BDI-II total score increased from 8.1 ± 6.2 at baseline to 10.3 ± 8.1 at the 5-year follow-up visit in PwP (p < 0.0001) but not in HC (from 4.1 ± 5.2 to 4.0 ± 5.7 [p = 0.896]). The prevalence of depression remained around 50–54% in the PwP group and 21–25% in the HC group throughout the follow-up period, but the mood state showed variability for each patient between visits. Patients’ QoL was associated with the depressive state throughout the entire follow-up period (p < 0.0001). Worsening QoL, sleep, longer disease duration, and an increase in neuropsychiatric symptoms were identified as independent factors associated with a worsening of mood over time in PwP (N = 348). Conclusions: Mood change over time in PwP is associated with QoL.

Background and objective: Depression is frequent in Parkinson's disease (PD), but it is unclear how mood changes and impacts patient's quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) over 5 years of follow-up, comparing it with a control group, as well as its relationship with the patients' QoL. Patients and Methods: PwP and healthy controls (HC) recruited from the COPPADIS cohort from January/2016 to November/2017 were included in this 5-year follow-up study. Mood was assessed by the Beck Depression Inventory II (BDI-II), and participants were classified as having major depression, minor depression, subthreshold depression, or non-depression at baseline and at 2, 4, and 5 years of follow-up. Correlation analysis and linear regression models were applied. Results: The BDI-II total score increased from 8.1 ± 6.2 at baseline to 10.3 ± 8.1 at the 5-year follow-up visit in PwP (p< 0.0001) but not in HC (from 4.1 ± 5.2 to 4.0 ± 5.7 [p=0.896]). The prevalence of depression remained around 50–54% in the PwP group and 21–25% in the HC group throughout the follow-up period, but the mood state showed variability for each patient between visits. Patients´ QoL was associated with the depressive state throughout the entire follow-up period (p< 0.0001). Worsening QoL, sleep, longer disease duration, and an increase in neuropsychiatric symptoms were identified as independent factors associated with a worsening of mood over time in PwP (N=348). Conclusion: Mood changes over time in PwP and are associated with QoL.

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.

Background and objective: Safinamide can improve the non-motor symptoms (NMSs) and quality of life (QoL) in patients with Parkinson’s disease (PD). In this post hoc analysis of the SAFINONMOTOR study, we analyzed the effect of safinamide on NMSs and QoL according to age, sex, disease duration (DD), and levodopa equivalent daily dose (LEDD). Patients and Methods: The change from baseline to the end of the observational period (6 months) in the Non-Motor Symptoms Scale (NMSS) and the 39-item Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) was analyzed in subgroups according to sex (male vs. female), age (≤75 vs. >75 years old), DD (≤10 vs. >10 years) and LEDD (≤1000 vs. >1000 mg). Nonparametric tests and general linear model (GLM) repeated measures were applied. Results: A total of 44 patients completed the final visit and were valid for the analysis. A significant reduction in the NMSS score was observed in all groups. Regarding QoL, a significant reduction in the PDQ-39 score was observed in females (p < 0.0001) and in patients with a DD > 10 years (p = 0.011) but not in males or those > 75 years old or receiving an LEDD > 1.000 mg. In the GLM, only LEDD at baseline influenced the degree of change in the NMSS total score (p = 0.026; F = 5.23). None of the variables influenced the change in the PDQ39. Conclusions: Safinamide improved NMSs independently of sex, age, DD, and LEDD. QoL improved independently of DD, and in females and non-elderly and very treated patients.

Background and objective: Safinamide improved non-motor symptoms (NMS) and quality of life (QoL) in 50 PD patients who participated in the SAFINOMOTOR study. In this post hoc analysis we analyzed the effect of safinamide on NMS and QoL according to sex, age, disease duration (DD) and levodopa equivalent daily dose (LEDD). Patients and Methods: The change from baseline to the end of the observational period (6 months) in the Non-Motor Symptoms Scale (NMSS) and the 39-item Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) was analyzed in subgroups according to sex (male vs. female), age (> 75 vs. ≤ 75 years old), DD (> 10 years vs. ≤ 10 years) and LEDD (> 1000 vs. ≤ 1000 mg). Nonparametric tests and general linear model (GLM) repeated measures were applied. Results: Forty-four PD patients completed the V6M visit and were valid for the analysis. A significant reduction in the NMSS was observed in all groups. Regarding QoL, a significant reduction in the PDQ-39 was observed in females (p< 0.0001) and in patients with a DD > 10 years (p=0.011) but not in males or those > 75 years old or receiving a LEDD > 1.000 mg. In the GLM, only LEDD at baseline influenced the degree of change in the NMSS total score (p=0.026; F=5.23). The decrease in the NMSS total scale was 43.8% for the group with a LEDD > 1.000 mg/day vs 33.7% for those ≤ 1.000 mg. None of the variables influenced the change in the PDQ39. Conclusion: Safinamide improved NMS independently of sex, age, DD and LEDD.

Background: Different screening tools to identify advanced Parkinson’s disease (APD) have emerged in recent years. Among them, wearable medical devices, such as STAT-ON™, have been proposed to help to objectively detect APD.Objectives: To analyze the correlation between STAT-ON™ reports and other assessment tools to identify APD and to assess the accuracy of screening tools in APD patients, using the STAT-ON™ as the gold standard.Methods: In this retrospective, observational study, data from the University Hospital Complex of Pontevedra database on 44 patients with potential APD who wore STAT-ON™ were extracted. Data were collected according to different sources of tools for identifying APD: (1) STAT-ON™, (2) information provided by the patient, (3) questionnaire for advanced Parkinson’s disease (CDEPA), (4) 5-2-1 Criteria, and (5) Making Informed Decisions to Aid Timely Management of Parkinson’s Disease (MANAGE-PD). Considering STAT-ON™ recordings as a reference, the sensitivity, specificity, and positive and negative predictive values for each tool were calculated. The kappa index assessed the degree of agreement between the gold standard and the other instruments.Results: Although no statistically significant association was found between STAT-ON™ recordings and any screening methods evaluated, the CDEPA questionnaire demonstrated the highest sensitivity and VPN values to detect patients with APD candidates for second-line therapy (SLT). According to the correlation analyses, MANAGE-PD demonstrated the highest degree of concordance with STAT-ON™ recordings to identify the SLT indication and to predict the SLT decision.Conclusion: STAT-ON™ device may be a helpful tool to detect APD and to guide treatment decisions.