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

Abstract

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 where 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 (e.g. 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 where 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 (e.g. cancer, multiple sclerosis).

Fatigue in Parkinson's disease: A systematic review and meta‐analysis

“…Our analyses further identified measurement instruments and cut‐off thresholds as moderators of prevalence estimates. These results encourage the systematic use of uniform diagnostic criteria for defining fatigue in PD, such as those recently proposed by Kluger and colleagues, in both clinical and research contexts. Given that fatigue prevalence rates in the general population range of 20% to 25%, the robust prevalence estimate of our meta‐analysis highlights the importance of assessing fatigue in PD, and suggests that, in most cases, fatigue in PD is likely attributable to disease‐related factors.…”

“…The lack of moderator effects for demographic and clinical factors on fatigue prevalence supports the view of fatigue as a disabling independent nonmotor symptom, which was confirmed by the separate meta‐analyses addressing the correlations between fatigue and other clinical features. Indeed, we observed quantitatively small (albeit significant) differences between fatigued and nonfatigued patients on age (around 1 year), disease duration (less than 1 year), LEDD (around 50 units), UPDRS‐III (∼5 points; this value is considered as denoting a minimal clinically important change in pharmacological trails), H & Yscore (0.33 points; this value is lower than 1 point representing the discrete unit of the H & Y scale), and cognitive performance (–0.66 points; this value is lower than 2 points, which is considered a threshold for defining a clinically significant difference on a 30‐point test).…”

Sleep-wake disturbances in the premotor and early stage of Parkinson's disease

“…As the disease progresses, fatigue becomes very prominent and disabling [78] and has a negative impact on quality of life [79]. The addition of dopaminergic medication seems to worsen its severity.…”

New Pharmacological Approaches to Treating Non-Motor Symptoms of Parkinson’s Disease

“…Fatigue was voted as the symptom most in need of further research by patients attending the 2013 World Parkinson’s Congress [51] and despite efforts to uncover a specific pathology, fatigue is not fully understood and there are few effective treatment options. Most studies find that fatigue affects 40% or more of PD patients and is one of the most underdiagnosed non-motor symptoms in PD [5, 52, 53].…”