The incidence and prevalence of Parkinson's disease (PD) is expected to raise dramatically over the next decades. Gender-related differences are not yet widely recognized, particularly regarding the ...response to dopaminergic medications. To analyse gender differences in the clinical effects of safinamide, compared to placebo, in Chinese PD patients of the pivotal XINDI trial. The XINDI study was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Patients were followed for 16 weeks receiving safinamide or placebo as add-on to levodopa. The primary efficacy endpoint was the change in the mean total daily OFF time. Secondary efficacy endpoints included total daily ON time, ON time with no/non-troublesome dyskinesia, Unified Parkinson's Disease Rating Scale and Parkinson's Disease Questionnaire-39 items. A post-hoc analysis was performed to describe the efficacy of safinamide in both genders on motor symptoms, motor fluctuations and quality of life. 128 (42%) out of 305 patients enrolled were women and 177 (58%) men. Our additional analyses of the XINDI study have shown that safinamide, compared to placebo, was associated with improvements in motor symptoms, motor fluctuations and quality of life in both genders, with some differences in the response that did not reach statistical significance, possibly due to sample size limitation and post-hoc design of the study. The changes from baseline at week 16 were > 50% higher in the females compared to males for the total daily OFF time (- 1.149 h vs - 0.764 h in males), the total daily ON time (1.283 h vs 0.441 h in males), the UPDRS total score (- 8.300 points vs - 5.253 points in males) and the UPDRS part II score (- 2.574 points vs - 1.016 points in males). The changes from baseline at week 16 were higher in the females compared to males in the "ADL" domain (- 6.965 points vs - 5.772 points in males), the "Emotional well-being" domain (- 6.243 points vs - 4.203 in males), the "Stigma" domain (- 6.185 points vs - 4.913 points in males) and the "Bodily discomfort" domain (- 5.196 points vs 1.099 points in males), while were higher in males in the "Mobility" score (- 6.523 points vs - 4.961 points in females) and the "Communication" score (- 3.863 points vs - 1.564 points in females). Safinamide was shown to improve PD symptoms and quality of life in both male and female Chinese patients. Possible differences in the response between genders need to be further studied in larger and different ethnic populations.
Diagnosis of multiple system atrophy (MSA) may be improved by using multimodal imaging approaches. We investigated the use of T1-weighted/T2-weighted (T1w/T2w) images ratio combined with voxel-based ...morphometry to evaluate brain tissue integrity in MSA compared to Parkinson's disease (PD) and healthy controls (HC). Twenty-six patients with MSA, 43 patients with PD and 56 HC were enrolled. Whole brain voxel-based and local regional analyses were performed to evaluate gray and white matter (GM and WM) tissue integrity and mean regional values were used for patients classification using logistic regression. Increased mean regional values of T1w/T2w in bilateral putamen were detected in MSA-P compared to PD and HC. The combined use of regional GM and T1w/T2w values in the right and left putamen showed the highest accuracy in discriminating MSA-P from PD and good accuracy in discriminating MSA from PD and HC. A good accuracy was also found in discriminating MSA from PD and HC by either combining regional GM and T1w/T2w values in the cerebellum or regional WM and T1w/T2w in the cerebellum and brainstem. The T1w/T2w image ratio alone or combined with validated MRI parameters can be further considered as a potential candidate biomarker for differential diagnosis of MSA.
Background and purpose
Very little is known about the progression of non‐motor symptoms (NMSs) in Parkinson's disease (PD) and there are no longitudinal studies exploring this topic from the earliest ...stage, when patients receive the diagnosis. We here report on the progression of NMSs over 4 years from diagnosis in a cohort of de‐novo, previously untreated, patients with PD.
Methods
Consecutive de‐novo (disease duration < 2 years), untreated patients with PD were enrolled in this observational study. Evaluations were then scheduled every 2 years and included assessment of motor and non‐motor features as well as of quality of life measures.
Results
Sixty‐one patients were prospectively followed‐up for 4 years from diagnosis. The majority of NMSs increased over time and significantly affected quality of life, whereas motor disability did not. There was no significant association between NMSs and dopaminergic therapy in terms of both drug class and total levodopa‐equivalent daily dosage. Excessive daytime sleepiness was the only NMS correlating with therapy with dopamine agonists. Female patients were more likely to have worse quality of life.
Conclusions
Non‐motor symptoms significantly increase over time, with a different progression rate for each one. NMSs significantly affect quality of life in PD and we here demonstrated that this was especially the case when patients were in their (motor) honeymoon period. Future trials should target non‐dopaminergic networks and consider NMSs in their outcomes.
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Background and purpose
Data suggest a relationship between sexual dysfunction, mainly erectile dysfunction in men, and worse disease progression in Parkinson's disease (PD). There is scant evidence ...on the correlates of sexual activity in PD patients. By involving a subgroup of 355 patients from the PRIAMO (Parkinson Disease Non Motor Symptoms) study, the present 24‐month longitudinal prospective analysis aims to demonstrate that the presence of active sexual life is associated with disease progression in early PD.
Methods and results
Multivariable mixed‐effect logistic regression models showed that gastrointestinal symptoms odds ratio 0.56, 95% confidence interval (CI) 0.39–0.82, P = 0.003 and apathy (odds ratio 0.42, 95% CI 0.29–0.63, P < 0.001) were less likely to be associated with sexual activity in men. Analysis also demonstrated that sexual activity in men was associated with lower motor disability (coefficient −2.881, 95% CI −4.732 to −1.030, P = 0.002), better quality of life (coefficient −24.196, 95% CI −44.884 to −3.508, P = 0.022; coefficient 0.083, 95% CI 0.023–0.143, P = 0.006) and lower depression scores (coefficient −1.245, 95% CI −2.104 to −0.387, P = 0.004). No association was shown in women.
Conclusions
This is the first prospective longitudinal study involving a large cohort of PD patients suggesting that sexual activity is associated with lower motor and non‐motor disability as well as with better quality of life in men. These findings should prompt movement disorders specialists to periodically inquiry about their patients’ sexual life.
•VoA – DBS is effective on both dystonia and tremor.•VoA – DBS benefits are not impaired by tolerance or side effects.•The variable VoA-DBS outcome previously reported were not proven by VTA ...simulation.•Application of new consensus on tremor classification may improve patient selection.
Background and purpose
Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative ...defences. Indeed, there is growing evidence of HO−bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression.
Methods
A cross‐sectional case−control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug‐naïve PD subjects and controls. Afterwards, PD subjects were included in a 2‐year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels.
Results
Seventy‐five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2‐year follow‐up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa‐equivalent daily dosage (P = 0.012) were found.
Conclusions
Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.
Background and purpose
New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non‐motor subtypes and models merging motor and non‐motor symptoms ...(NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non‐motor Symptoms) study, the present 24‐month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non‐motor burden as well as lower health‐related quality of life.
Methods and results
Multivariable mixed‐effect logistic regression models controlling for demographic and clinical variables showed that the following NMS domains were associated with urinary dysfunction: gastrointestinal odds ratio (OR) 2.57, 95% confidence interval (CI) 1.67–3.97, P < 0.001, cardiovascular (OR 2.22, 95% CI 1.18–4.17, P = 0.013), skin (OR 1.81, 95% CI 1.06–3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34–3.16, P = 0.001), pain (OR 1.85, 95% CI 1.21–2.83, P = 0.004), fatigue (OR 2.40, 95% CI 1.56–3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72–4.52, P < 0.001) and respiratory (OR 1.82, 95% CI 1.02–3.23, P = 0.039). Analysis also demonstrated that urinary dysfunction was associated with higher motor disability (coefficient 1.73, 95% CI 0.68–2.78, P = 0.001) and lower health‐related quality of life (coefficient −0.05, 95% CI −0.08 to −0.02, P < 0.001, and coefficient −3.49, 95% CI −5.21 to −1.77, P < 0.001) but not with more severe cognitive disability (coefficient −0.34, 95% CI −0.92 to 0.24, P = 0.251).
Conclusions
This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non‐motor disability as well as lower health‐related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.
FOG is a troublesome symptom of PD. Despite growing evidence suggesting that FOG in PD may be associated with cognitive dysfunction, the relationship between regional brain atrophy and FOG has been ...poorly investigated.
Optimized VBM was applied to 3T brain MR images of 24 patients with PD and 12 HC. Patients were classified as either FOG- or FOG+ (n = 12) based on their responses to a validated FOG Questionnaire and clinical observation. All patients with PD also underwent a detailed neuropsychological evaluation.
The VBM analysis in patients with FOG+ showed a reduced GM volume in the left cuneus, precuneus, lingual gyrus, and posterior cingulate cortex compared with both patients with FOG- and HC. We did not detect any significant change of GM volume when comparing HC versus all patients with PD (FOG- and FOG+). FOG clinical severity was significantly correlated with GM loss in posterior cortical regions. Finally, patients with FOG+ scored lower on tests of frontal lobe function.
Our findings provide the first evidence that the development of FOG in patients with PD is associated with posterior GM atrophy, which may play a role in the complex pathophysiology of this disabling symptom.
Gender is an important factor influencing epidemiological and clinical features of Parkinson’s disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs ...(miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman’s correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62;
p
< 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44;
p
< 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.
Background and purpose
Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the ...present study was to determine the progression of cognitive impairment in drug‐naïve untreated PD patients with or without clinically significant apathy.
Methods
Sixty‐two PD patients with a disease duration <2 years and without history of present or past therapy with pro‐dopaminergic agents were included and underwent the Apathy Evaluation Scale (S‐AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re‐evaluated on the S‐AES, a clinical interview and neuropsychological tests.
Results
According to the cut‐off value of the S‐AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow‐up (A+A+), nine patients had apathy only at follow‐up (A−A+), 37 patients never experienced apathy (A−A−) and eight patients showed apathy at the baseline only (A+A−). Cognitive performance significantly declined in all four groups. At both baseline and follow‐up A+A+ performed worse than A−A− on visuospatial and frontal tests; A−A+ had lower scores than A−A− on the interference task of the Stroop test (IT‐ST). Regression analysis showed that poor performance on the IT‐ST at baseline was the only independent predictor of onset of apathy at follow‐up.
Conclusions
The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT‐ST may predict development of apathy in PD patients.
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