Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation.

BACKGROUND AND PURPOSE: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). METHODS: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. RESULTS: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). CONCLUSIONS: Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Effectiveness and safety of safinamide in the Toledo Movement Disorders Unit. / Efectividad y seguridad de la safinamida en la Unidad de Trastornos de Movimiento de Toledo.

INTRODUCTION: The management of motor fluctuations in Parkinson's disease (PD) can be challenging, and current therapeutic options include the use of monoamine oxidase B inhibitors (MAO-B inhibitors), among others. The aim of this study was to evaluate the effectiveness and safety of safinamide in the clinical practice carried out in the Toledo Movement Disorders Unit. PATIENTS AND METHODS: This is a retrospective study in which data were collected at baseline and at six months from PD patients who were started on safinamide as an add-on therapy with a stable dose of levodopa in line with standard clinical practice. An analysis was performed by subgroups: patients who were given low-dose safinamide and patients who previously received rasagiline. RESULTS: Ninety patients (47 previously received rasagiline) completed the six-month follow-up. A statistically significant decrease in morning akinesia, nocturnal akinesia, wearing off, unpredictable off phenomenon and Unified Parkinson's Disease Rating Scale-III was observed both in those who previously received rasagiline and in those treated with low doses of safinamide. No variation was found in the dyskinesias. The adverse events described were mild, with generalised weakness, dizziness, nausea, headache and alopecia. CONCLUSIONS: Safinamide has been shown to be effective and safe in improving motor fluctuations, motor symptoms and the subjective perception of disease severity in PD patients previously receiving rasagiline and in those receiving low-dose safinamide, all of which is accompanied by a good safety profile.

TITLE: Efectividad y seguridad de la safinamida en la Unidad de Trastornos de Movimiento de Toledo.Introducción. El manejo de las fluctuaciones motoras en la enfermedad de Parkinson (EP) puede suponer un reto, que cuenta entre las diversas opciones terapéuticas actuales con el uso de inhibidores de la monoaminooxidasa B (IMAO-B), entre otros. El objetivo de este estudio fue evaluar la efectividad y seguridad de la safinamida en la práctica clínica de la Unidad de Trastornos de Movimiento de Toledo. Pacientes y métodos. Es un estudio retrospectivo en el que se registraron datos en una visita inicial y a los seis meses de pacientes con EP en los que se inició tratamiento con safinamida como terapia adicional con una dosis estable de levodopa según la práctica clínica habitual. Se realizó un análisis por subgrupos: pacientes que recibieron safinamida en dosis bajas y pacientes que recibieron previamente rasagilina. Resultados. Completaron los seis meses de seguimiento 90 pacientes (47 recibieron previamente rasagilina). Tanto en los pacientes que recibieron rasagilina previa como en los tratados con dosis bajas de safinamida se observó una disminución estadísticamente significativa de la acinesia matutina, la acinesia nocturna, el wearing off, el fenómeno off impredecible y la Unified Parkinson's Disease Rating Scale-III. No hubo variación en las discinesias. Los acontecimientos adversos descritos fueron leves, y se describieron sensación de debilidad generalizada, mareo, náuseas, cefalea y alopecia. Conclusiones. La safinamida ha demostrado ser eficaz y segura en la mejoría de fluctuaciones motoras, los síntomas motores y la percepción subjetiva de la gravedad de la enfermedad tanto en pacientes con EP que recibieron previamente rasagilina como en los que recibieron safinamida en dosis bajas, todo ello acompañado de un buen perfil de seguridad.

Clinical utility of a personalized and long-term monitoring device for Parkinson's disease in a real clinical practice setting: An expert opinion survey on STAT-ON™.

BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered "quite" to "very useful" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. CONCLUSION: STAT-ON™ could be a useful device for using in PD patients in clinical practice.

[Opicapone for the treatment of Parkinson's disease: real-life data in Spain]. / Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.

Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of "real world or real clinical practice" studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.

TITLE: Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.Resumen. La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de 'vida real o práctica clínica real'. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.

Depression is Associated with Impulse-compulsive Behaviors in Parkinson's disease.

BACKGROUND: Depression and impulse control disorders (ICDs) are both common in Parkinson's disease (PD) patients and their coexistence is frequent. Our aim was to determine the relationship between depression and impulsive-compulsive behaviors (ICBs) in a large cohort of PD patients. METHODS: PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were included in the study. The QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale) was used for screening ICDs (cutoff points: gambling ≥6, buying ≥8, sex≥8, eating≥7) and compulsive behaviors (CBs) (cutoff points: hobbyism-punding ≥7). Mood was assessed with the BDI-II (Beck Depression Inventory - II) and major, minor, and subthreshold depression were defined. RESULTS: Depression was more frequent in PD patients with ICBs than in those without: 66.3% (69/104) vs 47.5% (242/509); p<0.0001. Major depression was more frequent in this group as well: 22.1% [23/104] vs 14.5% [74/509]; p=0.041. Considering types of ICBs individually, depression was more frequent in patients with pathological gambling (88.9% [8/9] vs 50.2% [303/603]; p=0.021), compulsive eating behavior (65.9% [27/41] vs 49.7% [284/572]; p=0.032), and hobbyism-punding (69% [29/42] vs 49.4% [282/571]; p=0.010) than in those without, respectively. The presence of ICBs was also associated with depression (OR=1.831; 95%CI 1.048-3.201; p=0.034) after adjusting for age, sex, civil status, disease duration, equivalent daily levodopa dose, antidepressant treatment, Hoehn&Yahr stage, non-motor symptoms burden, autonomy for activities of daily living, and global perception of QoL. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Depression is associated with ICBs in PD. Specifically, with pathological gambling, compulsive eating behavior, and hobbyism-punding.

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Clinical utility of a personalized and long-term monitoring device for Parkinson's disease in a real clinical practice setting: An expert opinion survey on STAT-ON™.

BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered "quite" to "very useful" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. CONCLUSION: STAT-ON™ could be a useful device for using in PD patients in clinical practice.

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours: results from the COPPADIS cohort.

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.

Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression.

BACKGROUND: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. MATERIAL AND METHODS: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. RESULTS: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ±â€¯12.8 vs 11.6 ±â€¯10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ±â€¯0.5 vs 4 ±â€¯0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ±â€¯32 vs 29.1 ±â€¯25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. CONCLUSIONS: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.