Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To 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 METHODS: PD 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. RESULTS: The 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 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

Holter STAT-ON™ against other tools for detecting MF in advanced Parkinson's disease: an observational study.

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.

Vortioxetine Improves Depressive Symptoms and Cognition in Parkinson's Disease Patients with Major Depression: An Open-Label Prospective Study.

Depression is frequent in Parkinson's disease (PD) patients, but the evidence for many antidepressant agents to treat it in PD is insufficient. The aim of the present prospective open-label single-arm study (VOPARK, an open-label study of the effectiveness and safety of VOrtioxetine in PARKinson's disease patients with depression) was to analyze the effectiveness of vortioxetine on depressive symptoms in PD patients with major depression. The primary efficacy outcome was the change from baseline (VB) at the end of the observational period (12 weeks ± 14 days; V12w) in the 17-item Hamilton Depression Rating Scale (HAM-D17) total score. At VB, all patients had a HAM-D17 total score ≥16. A total of 30 patients (age 66.23 ± 10.27; 73.3% males) were included between February 2021 (first patient, 12/FEB/21) and March 2022 (last patient, 14/MAR/22). At 12 weeks, 27 patients completed the follow-up (90%). The total HAM-D17 total score was reduced by 52.7% (from 21.5 ± 4.75 at VB to 10.44 ± 7.54 at V12w; Cohen's effect size = −2.5; p < 0.0001) and the response and remission rates were 50% and 43.3%, respectively. Apathy (Apathy Scale; p < 0.0001), cognition (PD-Cognitive Rating Scale; p = 0.007), fatigue (Fatigue Severity Scale; p = 0.014), and quality of life (PDQ-39 (p = 0.001) and EUROHIS-QOL8 (p < 0.0001)) improved at 3 weeks as well. A total of 11 adverse events in 10 patients (33.3%) were reported, one of which was severe (vomiting related to vortioxetine with full recovery after drug withdrawal). Vortioxetine was safe and well tolerated and improved depressive symptoms and other non-motor symptoms in PD patients.

Safinamide improves sleep and daytime sleepiness in Parkinson's disease: results from the SAFINONMOTOR study.

BACKGROUND AND OBJECTIVE: Some studies observed a benefit of PD patients after treatment with safinamide in some non-motor symptoms. Our aim was to analyze the effectiveness of safinamide on sleep and daytime sleepiness in Parkinson's disease (PD) patients. MATERIAL AND METHODS: SAFINONMOTOR is a prospective open-label single-arm study conducted in 5 centers from Spain. In this analysis, a secondary objective of the study, the score in the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) at V1 (baseline) and V4 (6 months ± 1 month) were compared. RESULTS: Fifty patients were included between May/2019 and February/2020 (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The PSQI total score was reduced by 19.8% (from 10.43 ± 4.02 at V1 to 8.36 ± 4.41 at V4; p = 0.001). By domains, improvement was observed in subjective sleep quality (PSQI-C1; - 23.9%; p = 0.009), sleep latency (PSQI-C2; - 25%; p = 0.025), sleep duration (PSQI-C3; - 40%; p = 0.001), and habitual sleep efficiency (PSQI-C4; - 25.9%; p = 0.023). A significant reduction (- 24.7%) in the ESS total score from V1 to V4 was observed as well (from 9.20 ± 5.64 to 6.93 ± 5.11; p = 0.012). Specifically, the improvement in daytime sleepiness was observed in sitting and reading (p = 0.024) and sitting inactive in a public space (p = 0.027). A total of 21 adverse events in 11 patients (22%) were reported, 5 of which were severe (not related to safinamide). CONCLUSION: Safinamide was well-tolerated and improved sleep and daytime sleepiness in PD patients at 6 months.

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.

Effectiveness of Safinamide over Mood in Parkinson's Disease Patients: Secondary Analysis of the Open-label Study SAFINONMOTOR.

INTRODUCTION: Mood disorders are frequent in Parkinson's disease (PD) and a favorable effect of safinamide on mood has been observed. We aimed to analyze the effectiveness of safinamide on mood as a secondary objective from the SAFINONMOTOR (an open-label study of the effectiveness of SAFInamide on NON-MOTOR symptoms in patients with Parkinson's disease) study. METHODS: SAFINONMOTOR is a prospective open-label single-arm study conducted in five centers from Spain. Patients with PD were required to have at baseline a Non-Motor Symptoms Scale (NMSS) total score of at least 40. In this analysis, the changes from V1 (baseline) to V4 (6 months ± 1 month) in the BDI-II (Beck Depression Inventory-II), NMSS mood/apathy domain, and PDQ-39 (Parkinson's Disease Questionnaire-39) emotional well-being domain were analyzed. Depression was identified and classified (DSM-IV and Judd criteria) at baseline and at the end of follow-up as major depression (MD), minor depression (mD), subthreshold depression (subD), and non-depression (nonD). RESULTS: Fifty patients with PD were included (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis) and 44 patients (88%) completed the follow-up at 6 months. The BDI-II total score was reduced by 35.9% (from 15.88 ± 10.46 at V1 to 10.18 ± 6.76 at V4; p < 0.0001). A significant decrease in the NMSS mood/apathy domain and PDQ-39 emotional well-being domain was observed as well (p < 0.0001). At baseline, 52% of the patients presented MD, 34% mD, 12% subD, and 2% nonD whereas at V4 the percentages were 31.8%, 34.1%, 22.7%, and 11.4%, respectively (p = 0.029). CONCLUSIONS: Safinamide improves mood in patients with PD at 6 months.

Pain Improvement in Parkinson's Disease Patients Treated with Safinamide: Results from the SAFINONMOTOR Study.

BACKGROUND AND OBJECTIVE: Pain is a frequent and disabling symptom in Parkinson's disease (PD) patients. Our aim was to analyze the effectiveness of safinamide on pain in PD patients from the SAFINONMOTOR (an open-label study of the effectiveness of SAFInamide on NON-MOTOR symptoms in Parkinson´s disease patients) study. MATERIAL AND METHODS: SAFINONMOTOR is a prospective open-label single-arm study conducted in five centers from Spain. In this analysis, a secondary objective of the study, the score in the KPPS (King´s Parkinson´s Disease Pain Scale) at V1 (baseline) and V4 (6 months ± 1 month) were compared. Wilcoxon´s rank sum test was performed to test the changes from V1 to V4. RESULTS: Forty-four (88%) out of 50 PD patients (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis) completed the study. The KPPS total score was reduced by 43.6% (from 40.04 ± 36.18 in V1 to 22.60 ± 21.42 in V4; p < 0.0001). By domains, improvement was observed in musculoskeletal (-35.9%; p = 0.009), fluctuation-related (-51.7%; p = 0.020), nocturnal (-46.1%; p = 0.001), discoloration and/or edema/swelling (-50.4%; p = 0.009) and radicular pain (-40.1%; p = 0.048). A total of 21 adverse events in 11 patients (22%) were reported, five being severe, but not related to safinamide. CONCLUSION: Safinamide is well tolerated and improves pain in PD patients at 6 months. Future studies are necessary to analyze the possible beneficial effect of safinamide on pain in PD patients.

Safinamide Improves Non-Motor Symptoms Burden in Parkinson's Disease: An Open-Label Prospective Study.

Some studies observed a benefit of Parkinson's disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson's disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years; 58% females; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4; p < 0.0001). By domains, improvement was observed in sleep/fatigue (-35.8%; p = 0.002), mood/apathy (-57.9%; p < 0.0001), attention/memory (-23.9%; p = 0.026), gastrointestinal symptoms (-33%; p = 0.010), urinary symptoms (-28.3%; p = 0.003), and pain/miscellaneous (-43%; p < 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4; p < 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.