Outcomes Impacting Quality of Life in Advanced Parkinson’s Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel

Background: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. Objective: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and nonmotor symptoms. Methods: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL, and motor and nonmotor symptoms. Results: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. Conclusion: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.

Relationship between Motor and Nonmotor Symptoms and Quality of Life in Patients with Parkinson’s Disease

Background: Parkinson’s disease (PD) is a chronic neurodegenerative disease that implies a progressive and invalidating functional organic disorder, which continues to evolve till the end of life and causes different mental and physical alterations that influence the quality of life of those affected. Objective: To determine the relationship between motor and nonmotor symptoms and the quality of life of persons with PD. Methods: An analytic, descriptive, cross-sectional study was conducted with patients with different degrees of PD in the Albacete Health district. The estimated sample size required was 155 patients. The instruments used for data collection included a purpose-designed questionnaire and “Parkinson’s Disease Questionnaire” (PDQ-39), which measures eight dimensions and has a global index where a higher score indicates a worse quality of life. A descriptive and bivariate analysis was conducted (SPSS® IBM 24.0). Ethical aspects: informed consent and anonymized data. Results: A strong correlation was found between the number of motor and nonmotor symptoms and global health-related quality of life and the domains mobility, activities of daily living, emotional well-being, cognitive status, and pain (p < 0.05). Receiving pharmacological treatment and taking more than four medicines per day was significantly associated with a worse quality of life (p < 0.05). Patients who had undergone surgical treatment did not show better global quality of life (p = 0.076). Conclusions: All nonmotor symptoms and polypharmacy were significantly associated with a worse global quality of life.

Gender Was Associated with Depression but Not with Gastrointestinal Dysfunction in Patients with Parkinson’s Disease

Objective. To investigate the association between gender and gastrointestinal (GI) dysfunctions, as well as gender and other motor symptoms/nonmotor symptoms, in a sample of PD patients. Methods. 186 patients with PD were recruited into this study and divided into male PD group (M-PD) and female PD group (FM-PD). Demographic and PD-related clinical information of the participants were collected by the same neurologist. PD patients were objectively assessed by a spectrum of rating scales of motor symptoms and nonmotor symptoms (including GI dysfunctions). The data were analyzed by SPSS 20 statistical software. Results. Totally 95 cases (51.08%) were in the M-PD group and 91 cases (48.92%) in the FM-PD group. There were no significant differences in age, BMI, and lifestyles between the two groups (P > 0.05). Males had higher educational level (P = 0.002). Females were more likely to have early satiety and loss of appetite (P = 0.025, P = 0.001). There were no significant differences in LED disease duration, age of motor symptoms onset, types of motor symptoms onset, location of motor symptoms onset, and phenotype of motor symptoms between the two groups (P > 0.05). Females had significantly higher UPDRS-III and HAMD scores than males (P = 0.037, P = 0.034). There were no significant differences in PQSI, ESS, RLS, RBD, HAMA, HAMD, and MoCA scores between the two groups. Gender was associated with HAMD (OR = 0.682, P = 0.019). Conclusions. Gender is a risk factor for depression, but not for GI dysfunctions in patients with PD.

Relationship between coronavirus disease 2019 and Parkinson’s disease

New literature shows that COVID-19 has negative effects on patients with Parkinson’s disease (PD). COVID-19 is known to produce neurological manifestations and infects the central nervous system. Similarly, the virus also causes neuromuscular complications and involves the peripheral nervous system. Studies show PD patients with a severe COVID-19 infection have a higher mortality rate, worsening in symptoms, and require an increase in drug dosage. These studies suggest that COVID-19 may lead to a more rapid onset of PD, or may increase the risk of developing PD. Furthermore, researchers observed that Motor and nonmotor symptoms significantly worsened in PD patients with COVID compared to PD patients.

Fatigue in Patients With Multiple System Atrophy

Background and ObjectivesNonmotor symptoms are common in patients with multiple system atrophy (MSA), but there is limited knowledge regarding fatigue in MSA. This study aimed to investigate the frequency and evolution of fatigue and the factors related to fatigue and its progression in patients with MSA at an early stage.MethodsPatients with probable MSA were comprehensively evaluated at both baseline and the 1-year follow-up, including their motor and nonmotor symptoms. Fatigue and anxiety were assessed using the Fatigue Severity Scale (FSS) and Hamilton Anxiety Rating Scale (HARS), respectively. Orthostatic hypotension (OH) was defined as a decrease in the systolic or diastolic blood pressure by at least 30 and 15 mm Hg, respectively. The binary logistic regression model and linear regression model were used to analyze the factors related to fatigue and its progression, respectively.ResultsThis study enrolled 146 patients with MSA. The frequency of fatigue was 60.3%, 55.1%, and 64.9% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. The frequency of fatigue and the FSS score in patients with MSA increased from baseline to the 1-year follow-up (p < 0.05). Young age (odds ratio [OR] 0.939, 95% confidence interval [CI] 0.894–0.987), OH (OR 2.806, 95% CI 1.253–6.286), and high HARS score (OR 1.014, 95% CI 1.035–1.177) were associated with fatigue in MSA. OH was associated with fatigue in MSA-P (OR 3.391, 95% CI 1.066–10.788), while high HARS score was associated with fatigue in MSA-C (OR 1.159, 95% CI 1.043–1.287). In addition, only low FSS scores at baseline were associated with the annual progression rate of FSS scores in MSA, MSA-P, and MSA-C (p < 0.05). Neurofilament light chain, α-synuclein, glial fibrillary acidic protein, brain-derived neurotrophic factor, and triggering receptor expressed on myeloid cell-2 were not significantly associated with fatigue and its progression in MSA.DiscussionFatigue was prevalent in early-stage MSA, and it increased and remained persistent over time. This study demonstrated that OH and anxiety were associated with fatigue in patients with MSA.

Sex related differences in nonmotor symptoms of patients with idiopathic blepharospasm

Idiopathic blepharospasm shows a female predominance in prevalence, whether there are sex-related differences in distributions of nonmotor symptoms (NMSs) and predictors of quality of life are unknown. Four hundred and twenty-five patients with idiopathic blepharospasm were consecutively recruited, and underwent assessments including dystonia severity, mood disturbances, sleep disturbances, cognition, ocular symptoms, and quality of life. Frequencies and distributions of NMSs, and predictors of quality of life in female and male patients were investigated. NMSs existed in majority of male (94.0%) and female (95.8%) patients. The frequencies of depression, cognition dysfunction, and poor sleep quality were higher in female patients, while the frequency of excessive daytime sleepiness was higher in male patients. More female (79.5%) patients had multiple NMS domains affected than male (70.1%) patients (p = 0.040). Quality of life was associated with depression, anxiety and motor severity for female patients (adjusted R2 = 0.367, p < 0.001), while associated with depression, excessive daytime sleepiness and motor severity for male patients (adjusted R2 = 0.430, p < 0.001). The highly prevalent coexistence of multiple NMSs found in patients with blepharospasm support that blepharospasm is a network disorder. The sex-related differences in the pattern of NMSs and predictors of quality of life may aid the development of tailored management of blepharospasm.

TrkA Signalling and Parkinson’s Dementia

Cognitive impairment and dementia are the most frequently occurring nonmotor symptoms in Parkinson’s disease (PD), yet these symptoms are mostly overlooked and are not diagnosed and treated exceptionally like the cardinal motor symptoms in clinical practice. It is only in the late twentieth century that dementia has been recognized as a major clinical manifestation in PD. The possible mechanisms that cause dementia are complex with different patterns of cognitive behavior that disrupt the patient’s quality of life. It is preeminently considered that the cholinergic denervation in the basal forebrain region mediates dementia in PD. So far, dopamine-based therapy is the key objective in the treatment of PD and the nonmotor symptoms are mostly neglected. Interestingly, the loss of Tyrosine kinase receptor-A (TrkA) signaling in basal forebrain results in neuronal atrophy, which precedes cholinergic denervation and cognitive impairment. Nerve Growth Factor (NGF) binds to TrkA receptors, inducing a cascade of events like PI-3Kinase/Akt and MAPK signaling pathways that render cholinergic degeneration and upregulate the choline acetyltransferase activity and neuronal differentiation. Hence, TrkA receptor activation by small molecules might attenuate the dementia symptoms associated with PD, and may be targeted as a novel treatment strategy along with regular clinical agents.

Caffeine consumption and Parkinson’s disease: a mini-review of current evidence

In the absence of efficient disease-modifying treatments for Parkinson’s disease (PD), research has focused on identifying potential environmental factors whose modulation may prevent or slow the progression of this neurodegenerative disorder. Compelling epidemiological evidence suggests that caffeine consumption is inversely associated with the risk of developing PD. Further experimental findings demonstrated that caffeine, by particularly targeting adenosine A2A (A2AR) receptors, protected PD animal models against the loss of dopaminergic neurons. The antagonistic action of caffeine on adenosine receptors not only slowed PD-related neurodegeneration, but also improved motor and nonmotor symptoms of PD in animal models. Here, we review the potential action mechanisms by which caffeine might play a role in reducing the risk of PD. We also review current evidence of the benefits of caffeine consumption in motor and nonmotor symptoms of PD. Finally, we point out how these promising findings could lead to the identification of new approaches for effective treatment of PD.