Parkinson's disease-related fatigue: A case definition and recommendations for clinical research.

Fatigue is one of the most common and disabling symptoms in Parkinson's disease (PD). Since fatigue was first described as a common feature of PD 20 years ago, little progress has been made in understanding its causes or treatment. Importantly, PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. In response, the Parkinson Disease Foundation and ProjectSpark assembled an international team of experts to create recommendations for clinical research to advance this field. The working group identified several areas in which shared standards would improve research quality and foster progress including terminology, diagnostic criteria, and measurement. Terminology needs to (1) clearly distinguish fatigue from related phenomena (eg, sleepiness, apathy, depression); (2) differentiate subjective fatigue complaints from objective performance fatigability; and (3) specify domains affected by fatigue and causal factors. We propose diagnostic criteria for PD-related fatigue to guide participant selection for clinical trials and add rigor to mechanistic studies. Recommendations are made for measurement of subjective fatigue complaints, performance fatigability, and neurophysiologic changes. We also suggest areas in which future research is needed to address methodological issues and validate or optimize current practices. Many limitations in current PD-related fatigue research may be addressed by improving methodological standards, many of which are already being successfully applied in clinical fatigue research in other medical conditions (eg, cancer, multiple sclerosis). © 2016 International Parkinson and Movement Disorder Society.

Improvement in Parkinson Disease Symptoms After Treatment for COVID-19 with Monoclonal Antibodies.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by motor symptoms, such as bradykinesia, and non-motor symptoms, such as fatigue, which can be a particularly disabling feature of the disease. METHODS: We conducted a retrospective chart review on a patient who reported improvement in baseline PD symptoms after COVID-19 treatment. RESULTS: The patient is a 76-year-old male with a six-year history of PD who developed a COVID-19 infection, underwent treatment with COVID-19 monoclonal antibodies, and experienced a remarkable improvement in his pre-COVID PD symptoms, most notably his gait and fatigue. Prior to COVID, he rated his fatigue as '9 out of 10,' which worsened to 10 out of 10 during his COVID infection, and post-COVID treatment, his fatigue improved to '3 out of 10'. PRINCIPAL CONCLUSIONS: We described an unexpected improvement in baseline PD symptoms for a patient treated with COVID-19 monoclonal antibodies. Further investigation will be essential to understand the mechanisms underlying this phenomenon.

Predictors and course of health-related quality of life in Parkinson's disease.

We investigated how health related quality of life (HRQL) changes over time in a population-based cohort of patients with Parkinson's disease (PD), and which factors predict a lower level of HRQL in these patients. Of 227 patients with PD assessed at baseline and followed prospectively, information on HRQL-status was obtained in 111 subjects 4 years and 82 patients 8 years after inclusion. HRQL was measured by the Nottingham Health Profile (NHP). Analyses were conducted using generalized estimating equation models. The NHP total score (P < 0.001) and scores in all NHP dimensions except for sleep worsened significantly during follow-up. Steepest slope was found for the domain physical mobility (3.16, 95% CI 2.39-3.92), followed by the domains social isolation (2.22, 95% CI 1.52-2.93) and emotional reactions (1.36, 95% CI 0.74-1.97). In addition to follow-up time, higher Hoehn and Yahr staging, higher Montgomery and Aasberg Depression Rating Scale scores, and presence of insomnia at baseline were associated with lower levels of overall HRQL during follow-up. We conclude that PD has an increasing impact on HRQL as the disease progresses. During long-term follow-up, deterioration in physical mobility was the most important single factor contributing to decline in HRQL in our cohort, although distress of nonmotor character as a whole outweighed the impact of distress in physical mobility on overall HRQL. More advanced disease, higher severity of depressive symptoms, and presence of insomnia were found to be important and independent predictors of poor HRQL. (c) 2008 Movement Disorder Society.

Fatigue in Parkinson's disease.

Fatigue is one of the most common nonmotor symptoms in Parkinson's disease and may affect a wide range of everyday activities, cause disability and reduce quality of life. It occurs at every stage of PD, and once present will often persist and may worsen over time. Lack of a consensus of definition and classification, and a range of different self-reporting scales has so far made the study of fatigue challenging. We review a unifying taxonomy for defining fatigue in clinical and research contexts as well as case definition criteria for PD-related fatigue. The potential causes of fatigue in PD are discussed as are recommendations for treatment.

Is fatigue associated with cognitive dysfunction in early Parkinson's disease?

INTRODUCTION: Fatigue is a common and disabling symptom which may be seen in early Parkinson's disease (PD). Our understanding of the phenomenology and etiology of fatigue in PD is limited. The objective of this study was to determine whether fatigue was related to cognition in early PD patients. METHODS: The study is part of the Norwegian ParkWest project, a population-based cohort study, comprising 184 de novo, drug-naïve patients with PD. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Cognition was assessed by a battery of tests evaluating functions in the domains of verbal memory, processing speed, executive function and visuospatial abilities. RESULTS: 107 of the cohort had moderate to severe fatigue (FSS ≥ 4). In univariate correlation analyses high fatigue score was correlated to disease severity, presence of sleep problems, depressive symptoms, apathy, reduced processing speed and reduced visuospatial abilities. In a multiple regression analysis only disease severity (measured by the UPDRS part 3), sleep problems, depressive symptoms and reduced visuospatial abilities contributed to the model. CONCLUSION: Fatigue is associated with visuospatial function in early PD patients. Further studies are needed to determine the pathophysiologic relevance of this association.

Fatigue in Parkinson's disease: report from a mutidisciplinary symposium.

Fatigue is a severe problem for many people living with Parkinson's disease (PD). Best estimates suggest that more than 50% of patients experience this debilitating symptom. Little is known about its etiology or treatment, making the understanding of fatigue a true unmet need. As part of the Parkinson's Disease Foundation Community Choice Research Program, patients, caregivers, and scientists attended a symposium on fatigue on 16 and 17 October 2014. We present a summary of that meeting, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from multiple sclerosis (MS), depression, and cancer-disorders in which fatigue figures prominently too. We conclude with focused recommendations to enhance our understanding and treatment of this prominent problem in PD.

Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson's disease.

BACKGROUND: The relative impact of motor- and non-motor symptoms on health-related quality of life in early Parkinson's disease is poorly documented. METHODS: 188 patients with incident Parkinson's disease from a population-based study were examined at the time of diagnosis, before initiation of dopaminergic treatment, with follow-up of 166 patients three years later. Health-related quality of life was assessed by the 36-item Short-form Health Survey (SF-36). Motor and non-motor variables were derived from the Unified Parkinson's disease rating scale and other established scales. RESULTS: Multiple regression analyses showed that the non-motor symptoms strongest associated with reduced SF-36 scores at diagnosis and three years later were depression, fatigue and sensory complaints. The motor symptoms most related to impaired SF-36 scores were problems with gait and activities of daily living that cover personal needs. The variance of SF-36 mental summary scores was much better explained by non-motor vs. motor symptoms, both at baseline (R(2) = 0.384 vs. 0.095) and 3 years later (R(2) = 0.441 vs. 0.195). Also SF-36 physical summary scores were better explained by non-motor vs. motor symptoms with R(2) = 0.372 vs. 0.322 at baseline and R(2) = 0.468 vs. 0.315 after 3 years. CONCLUSION: In early PD, including the phase before dopaminergic treatment is initiated, non-motor symptoms are more important for reduced health-related quality of life than motor symptoms. Fatigue, depression, sensory complaints and gait disturbances emerge as the most relevant symptoms and should be given corresponding attention in the management of patients with early PD.

Mortality and Parkinson disease: A community based study.

OBJECTIVE: To compare the mortality of a community-based cohort of patients with carefully diagnosed Parkinson disease (PD) with the mortality in an age-matched population from the same study area and to investigate the possible influence of clinical features and diagnostic accuracy on survival in PD. METHODS: A total of 245 patients with PD were identified and included in the study. Patients were classified into groups of clinical definite, probable, and possible PD. The study period was 8 years. A total of 142 patients died. The mortality rates for the Norwegian population, which were available in 1-year intervals for all birth cohorts and both sexes during the study period, were used as controls. RESULTS: The standardized mortality ratio (SMR) for the total patient group was 1.52. The mortality rate was increased for both sexes (male SMR = 1.54, female SMR = 1.49) and in all age groups at disease onset (<60 years SMR = 1.92, 60 to 70 years SMR = 1.50, >70 years SMR = 1.41). The survival of patients with clinical definite PD was only modestly reduced (SMR = 1.35), whereas the SMR for possible PD was as high as 1.99. CONCLUSIONS: Our study gives evidence for increased mortality in PD despite modern treatment. The increase is not extensive in patients with a high probability for idiopathic PD.