Background 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.
Hypomimia in Parkinson’s disease (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. Hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit where motor and non‐motor aspects converge.
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.
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.
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.
In this cohort of PwPD with motor fluctuations, the response to levodopa did not weaken after a 4-year follow-up.
•A good response to levodopa is a key factor to indicate device-aided or on-demand therapies in Parkinson's disease.•Response to levodopa did not weaken after a 4-year follow-up in 63 fluctuators PD patients.•On and off scores worsen at the expense of axial symptoms and in parallel with conservation of the levodopa response.•There were no differences by motor phenotype.
Background
Although dopamine agonists (DAs) are useful in Parkinson′s disease (PD), they are not frequently used in elderly patients due to adverse effects. However, there is a lack of evidence ...because few elderly PD patients are enrolled in clinical trials.
Aims of the study
The aims of this study were to analyze the reasons of DA withdrawal (DAW) in a group of PD patients in clinical practice and to identify the related factors. Specifically, we studied the effect of age, comorbidity, and polypharmacy as potential risk factors for DAW.
Methods
A retrospective chart review of the follow‐up (from May, 2012 to March, 2015) of a subgroup of PD patients receiving a DA (n = 68; 60.3% males, 69.3 ± 9.2 years old) from a cohort (n = 150) previously studied in detail in 2012 was used to identify predictive factors of DAW.
Results
The DAW percentage was 18.2% (12/66; follow‐up of 690.2 ± 232.6 days). DAW causes were cognitive impairment (3), reduction therapy (3), hallucinations (2), dyskinesia (2), and excessive diurnal somnolence (2). Only a higher levodopa daily dose (HR 1.003; 95% CI 1.001–1.006; P = 0.044) was an independent predictor of DAW after adjustment for other explanatory variables.
Conclusions
The frequency of DAW was low. Advanced age alone is not a contraindication to the administration of DAs.
The frequency of dopamine agonist withdrawal in clinical practise is low and not related to age. A higher levodopa dose predicts higher risk of dopamine agonist withdrawal.
The evaluation of patients with Parkinson's disease (PD) is complex and the detection of non-motor symptoms by the neurologist a very important aspect. However, it takes time and is not easy in daily ...clinical practice. As an alternative, a trained nurse can perform this evaluation.
To describe the non-motor evaluation of the patients from the Cohort of Patients with Parkinson's Disease in Spain, 2015 study (COPPADIS-2015) conducted by movement disorder specialist nurse from our centre.
Patients and caregivers from the COPPADIS-2015 study were included. The assessment included: (1) cognition (PD-CRS and puzzle test); (2) non motor symptoms as a whole (NMSS); (3) mood (BDI-II); (4) sleep (PDSS); (5) neuropsychiatric symptoms (NPI, QUIP-RS); (6) pain and fatigue (VAS); 7) gait problems (FOGQ); 8) disability (ADLS); 9) quality of life (PDQ-39SI, PQ-10, WHOQL-8); (10) caregiver status (ZCBI, CSI, BDI-II, PQ-10, WHOQL-8).
102 patients (65.3±8.2 y; 52% males) and 62 caregivers were evaluated between January 2016, and October, 2017. Mean time of non-motor evaluation was 73.7±20.5min. Twenty-three point five percent of the patients had cognitive impairment, 17.6% major depression, 14.7% impulse control disorder, and 66.7% pain.
The non-motor assessment of patients with PD takes a long time but is very valuable given that it provides a great deal of information about the patient's condition and can be done by trained nurses.
La evaluación de los pacientes con enfermedad de Parkinson (EP) es compleja siendo fundamental para el neurólogo detectar diferentes síntomas no motores. Sin embargo, lleva tiempo y no es fácil en la práctica diaria. Como alternativa, una enfermera entrenada puede realizar dicha evaluación.
Describir la evaluación no motora llevada a cabo por la enfermera especialista en trastornos del movimiento dentro del proyecto de investigación Cohort of Patients with Parkinson's DIsease in Spain, 2015 (COPPADIS-2015) en nuestro centro (CHUF).
Se incluyeron pacientes con EP así como cuidadores principales que cumplieran con los criterios de participación del estudio COPPADIS-2015. La evaluación llevada a cabo por la enfermera incluía: 1) cognición (PD-CRS y test del puzle); 2) SNM en general (NMSS); 3) estado de ánimo (BDI-II); 4) sueño (PDSS); 5) síntomas neuropsiquiátricos (NPI, QUIP-RS); 6) dolor y fatiga (VAS-Pain y VAS-Fatigue); 7) alteraciones de la marcha (FOGQ); 8) autonomía (ADLS); 9) calidad de vida (PDQ-39SI, PQ-10, WHOQL-8); 10) estado del cuidador (ZCBI, CSI, BDI-II, PQ-10, WHOQL-8).
Un total de 102 pacientes (65,3±8,2 años; 52% varones) con EP y 62 cuidadores fueron evaluados entre enero de 2016 y octubre de 2017. El tiempo medio de evaluación fue de 73,7±20,5 min. El 23,5% de los pacientes presentaba deterioro cognitivo, 17,6% depresión mayor, 14,7% trastorno de control de impulsos y 66,7% dolor.
La evaluación no motora de los pacientes con EP consume tiempo pero es muy valiosa dado que proporciona gran información del estado del paciente y puede ser llevada a cabo por personal de enfermería entrenado.
Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal ...homocysteine levels to cortical degeneration in PD remains elusive.
To characterize the cortical structural correlates of homocysteine levels in PD.
From the COPPADIS cohort, we identified a subset of PD patients and healthy controls (HC) with available homocysteine and imaging data. Surface-based vertex-wise multiple regression analyses were performed to investigate the cortical macrostructural (cortical thinning) and microstructural (increased intracortical diffusivity) correlates of homocysteine levels in this sample.
A total of 137 PD patients and 43 HC were included. Homocysteine levels were increased in the PD group (t = −2.2, p = 0.03), correlating in turn with cognitive performance (r = −0.2, p = 0.03). Homocysteine in PD was also associated with frontal cortical thinning and, in a subset of patients with available DTI data, with microstructural damage in frontal and posterior-cortical regions (p < 0.05 Monte-Carlo corrected).
Homocysteine in PD appears to be associated with cognitive performance and structural damage in the cerebral cortex. These findings not only reinforce the presence and importance of cortical degeneration in PD, but also suggest that homocysteine plays a role among the multiple pathological processes thought to be involved in its development.
•Parkinson's disease (PD) patients appear to show increased homocysteine levels.•Homocysteine correlated in turn with cognitive performance in our PD sample.•Homocysteine was also associated with cortical macro- and microstructural alterations.•This metabolic marker may play a role in cortical degeneration in the PD population.
We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.
The study included ...a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models.
Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02).
Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.
•Multimodal MRI study of cognitive deficits in nondemented Parkinson's disease (PD).•Cognitive deficits in PD relate to lower cholinergic basal forebrain (CBF) volume.•Hippocampal volume not associated with cognitive deficits.•DTI diffusion measures more sensitive than volume in hippocampus but not in CBF.•Implications for the development of imaging biomarkers of cognitive decline in PD.
Background 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.
Recently, it has been reported that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on 4 axes (Motor; Non‐motor; Cognition; Dependency) and 5 stages, correlated with disease severity and patients' quality of life. In this new manuscript, we observed that staging PD according to the MNCD classification correlated with caregivers' strain and burden.
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.
Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD.
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.
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;
= 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11;
= 0.259). Symptoms such as depression (
< 0.0001), fatigue (
< 0.0001), and pain (
< 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (
< 0.0001), speech problems (
< 0.0001), rigidity (
< 0.0001), and hypersexuality (
< 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (
= 0.002). Perception of quality of life was generally worse in females (PDQ-39,
= 0.002; EUROHIS-QOL8,
= 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (
= 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (
= 0.001).
The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
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