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

Parkinson’s disease; Non-motor symptoms; SexMalaltia de Parkinson Símptomes no motors; SexeEnfermedad de Parkinson; Síntomas no motores; SexoBackground 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.COPPADIS and the present study were developed with the help of Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético ( https://fundaciondegen.org/) and Alpha Bioresearch (www.alphabioresearch.com). Also, we received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”) to develop a part of the COPPADIS project

Diplopia is frequent and associated with motor and non-motor severity in Parkinson’s disease: results from the COPPADIS cohort at 2-year follow-up

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

Changes in Principal Caregiver Mood Affects the Mood of the Parkinson’s Disease Patient: The Vicious Cycle of Illness

Caregiver; Parkinson’s disease; Quality of lifeCuidador; Malaltia de Parkinson; Qualitat de vida.Cuidador; Enfermedad de Parkinson; Calidad de vidaThe aim of this study was to analyze how the change in the caregiver’s status influences PD patients. PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centersin Spain from the COPPADIS cohort were included in the study (V0). They were evaluated again at 2-year follow-up(V2). 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 V0 and V2. Multivariate models were used to analyze the impact of the change from V0 to V2 (_) on the caregiver’s status over the change in the patient’s status. BDI-II and _EUROHIS-QOL8 in the caregiver predicted _BDI-II (_ = 0.32; p < 0.0001; R2 = 0.71) and _EUROHIS-QOL8 (_ = 0.39; p < 0.0001; R2 = 0.68) in the patient, respectively. Variables related to the caregiver were not associated with changes in the patient´s health-related QoL (_PDQ-39 [39-item Parkinson’s disease Questionnaire]) or autonomy for activities of daily-living (_ADLS [Schwab & England Activities of Daily Living Scale]). The change in the caregiver’s mood and global QoL was associated with the change in the patient’s mood and global QoL, respectively, independently of other variables of the disease influencing both patient´s aspects. Based on this finding, it could be of great importance to detect depression in the principal caregiver of a patient and act on it as earlier as possible.COPPADIS and the present study were developed with the help of Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético (https://fundaciondegen.org/) and Alpha Bioresearch (www.alphabioresearch.com). Also, we received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017-2020 por el Proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”) to develop a part of the COPPADIS project

Risk of Cognitive Impairment in Patients With Parkinson’s Disease With Visual Hallucinations and Subjective Cognitive Complaints

Cognitive impairment; Parkinson's disease; Visual hallucinationsDeterioro cognitivo; Enfermedad de Parkinson; Alucinaciones visualesDeteriorament cognitiu; Malaltia de Parkinson; Al·lucinacions visualsBackground and Purpose Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson’s disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson’s disease and normal cognition (PD-NC). Methods Patients with PD-NC (total score of >80 on the Parkinson’s Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as “with SCC” and “with VH,” respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81. Results At V0 (n=376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p<0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05–6.83, p=0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36–10.17, p=0.011). Conclusions VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC.The resources obtained for the development of this project have been obtained by the Degen Foundation (https://fundaciondegen.org/). A part of the Project is financed with grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017-2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”)

Motor Fluctuations Development Is Associated with Non-Motor Symptoms Burden Progression in Parkinson’s Disease Patients: A 2-Year Follow-Up Study

Parkinson’s disease; Motor fluctuations; Non-motor symptomsEnfermedad de Parkinson; Fluctuaciones motoras; Síntomas no motoresMalaltia de Parkinson; Fluctuacions motrius; Símptomes no motorsThe aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson’s disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up

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

Prevalence; Drooling; Parkinson's diseasePrevalencia; Babeo; Enfermedad de parkinsonPrevalència; Babeig; Malaltia de parkinsonIntroduction. 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;  < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls;  < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032;  = 0.012), being male (OR = 2.333;  < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020;  < 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;  < 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;  = 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.COPPADIS and the present study were developed with the help of Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético (https://fundaciondegen.org/) and Alpha Bioresearch (https://www.alphabioresearch.com). Also, The authors received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”) to develop a part of the COPPADIS project. The authors would like to thank all patients and their caregivers who collaborated in this study. They would also like to thank Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético (https://fundaciondegen.org/) and Alpha Bioresearch (https://www.alphabioresearch.com) and other institutions for helping them

Staging Parkinson’s disease according to the MNCD classification correlates with caregiver burden

Malaltia de Parkinson; Cuidador; Símptomes no motorsParkinson's disease; Caregiver; Non-motor symptomsEnfermedad de Parkinson; Cuidador; Síntomas no motoresBackground and objective: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients’ quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. Patients and methods: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Two hundred and twenty-four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4–5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ-10 (p = .001), but no significant differences were observed in the BDI-II (p = .310) and EUROHIS-QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI-II (r = .306; p < .0001) in caregivers.Conclusion: Staging PD according to the MNCD classification is correlated with caregivers’ strain and burden.Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético; Alpha Bioresearch; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: PI16/0157

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease

Altres ajuts: acord transformatiu CRUE-CSICBackground and purpose: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. Methods: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. Results: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (β = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. Conclusion: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge

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

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 HΨ Patients with a lower H&Y stage may be more affected if they have a greater NMS burden