Response to levodopa in Parkinson's disease over time. A 4-year follow-up study.

BACKGROUND AND OBJECTIVE: A good response to levodopa is a key factor to indicate device-aided therapies in people with Parkinson's disease (PwPD). The aim of the present study was to analyze the response to levodopa in PwPD with motor fluctuations followed for 4 years. PATIENTS AND METHODS: PwPD with motor fluctuations recruited from January 2016 to November 2017 from the COPPADIS cohort and assessed annually (from baseline to 4-year follow-up) during the OFF and ON states were included in this analysis. At each visit, the Unified Parkinson's Disease Rating Scale - part III (UPDRS-III) was applied during the OFF state (without medication during the last 12 h) and during the ON state. General linear model repeated measures were used to test for changes in the mean UPDRS-III-OFF, UPDRS-III-ON, and ΔUPDRS-III (UPDRS-III-OFF - UPDRS-III-ON) between visits. Levodopa equivalent daily dose (LEDD) was included as covariate. RESULTS: Sixty-three patients (63.94 ± 8.42 years old; 68.3% males) were included. Mean disease duration was 7.81 ± 3.64 years. From baseline to 4-year follow-up visit, a significant increase in both the UPDRS-III-OFF (from 27.98 ± 9.58 to 31.75 ± 12.39; p = 0.003) and the UPDRS-III-ON (from 15.92 ± 7.93 to 18.84 ± 8.17; p = 0.006) was observed despite the significant increase in the LEDD (from 896.35 ± 355.65 to 1085.51 ± 488.29; p = 0.003). However, no significant differences were detected between visits in the ΔUPDRS-III. CONCLUSION: In this cohort of PwPD with motor fluctuations, the response to levodopa did not weaken after a 4-year follow-up.

Cognitive impairment and dementia in young onset Parkinson's disease.

BACKGROUND AND OBJECTIVE: Patients with young-onset Parkinson's disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls. PATIENTS AND METHODS: Patients with Parkinson's disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson's Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65-80 mild cognitive impairment (MCI). RESULTS: One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson's Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R2 = 0.61; OR = 0.965; p = 0.029). CONCLUSION: Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients.

Suicidal ideation among people with Parkinson's disease and comparison with a control group.

BACKGROUND: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. METHODS: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI. RESULTS: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041). CONCLUSION: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.

Prevalence and Factors Associated with Drooling in Parkinson's Disease: Results from a Longitudinal Prospective Cohort and Comparison with a Control Group.

Introduction: Drooling in Parkinson's disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. 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-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results: The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p = 0.007) as a predictor of drooling at V2. Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.

Staging Parkinson's Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life.

BACKGROUND: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). OBJECTIVE: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. METHODS: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. CONCLUSION: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.

Sex Differences in Motor and Non-Motor Symptoms among Spanish Patients with Parkinson's Disease.

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.

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.

Predictors of the change in burden, strain, mood, and quality of life among caregivers of Parkinson's disease patients.

BACKGROUND AND OBJECTIVE: Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes. PATIENTS AND METHODS: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied. RESULTS: Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; ß = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (ß = 0.416; p < 0.0001), CSI (ß = 0.277; p = 0.001), and EUROHIS-QOL (ß = 0.397; p = 0.002). CONCLUSION: Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase.