Fatigue Management in Parkinson's Disease

Fatigue in Parkinson’s disease represents a pervasive non-motor symptom that significantly diminishes quality of life and functional independence. It encompasses both physical and mental dimensions and arises from multifactorial mechanisms, including neurotransmitter imbalances, cortical excitability deficits and altered network connectivity. Effective management requires a personalised, multidisciplinary approach combining pharmacological optimisation—such as tailored dopaminergic regimes and adjunctive agents targeting monoamine and glutamate pathways—with non-pharmacological strategies, including structured exercise, vestibular and cognitive rehabilitation, sleep hygiene and behavioural interventions. Reliable assessment tools and emerging biomarkers from neuroimaging and biofluid studies can guide treatment decisions and monitor response. By integrating mechanistic insights with practical therapeutic options, clinicians can mitigate fatigue’s impact, improve daily functioning and address a major unmet need in global Parkinson’s care.

Research from Nature Portfolio

Foundational work has elucidated the interplay between serotonergic dysfunction and iron homeostasis in mental fatigue. Patients exhibiting high fatigue scores showed reduced cerebrospinal serotonin alongside elevated iron and transferrin levels, with mental fatigue correlating negatively with serotonin and positively with iron markers. These findings exposed central and peripheral serotonin pathways and iron regulation as viable targets for future interventions aimed at alleviating fatigue symptoms.

Fatigue Management in Parkinson's Disease publication trend

The graph below shows the total number of articles in fatigue management in parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Fatigue Severity Scale (FSS): A patient-reported questionnaire evaluating the impact of fatigue on daily activities.

Degree Centrality: A graph-theory metric measuring the number of direct connections a brain region has within a functional network.

Precuneus: A medial parietal lobe structure implicated in sensorimotor integration and attentional processes.

MAO-B inhibitor: A drug class that blocks monoamine oxidase B to preserve synaptic dopamine levels.

Postural Instability and Gait Difficulty (PIGD): A clinical subtype of Parkinson’s characterised by balance impairment and walking difficulties.

Transferrin: An iron-transport protein involved in systemic and central nervous system iron regulation.

Cerebrospinal Fluid (CSF): The fluid surrounding the brain and spinal cord, used for biomarker analysis.

References

1. Aberrant voxel‐based degree centrality and functional connectivity in Parkinson's disease patients with fatigue. CNS Neuroscience & Therapeutics (2023).
2. Characteristics of fatigue in Parkinson’s disease: A longitudinal cohort study. Frontiers in Aging Neuroscience (2023).
3. Fatigue in fluctuating Parkinson’s disease patients: possible impact of safinamide. Journal of Neural Transmission (2023).
4. Fatigue in Parkinson’s disease: report from a multidisciplinary symposium. npj Parkinson's Disease (2016).
5. Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease. Scientific Reports (2016).
6. Effects of Vestibular Rehabilitation on Fatigue and Activities of Daily Living in People with Parkinson’s Disease: A Pilot Randomized Controlled Trial Study. Parkinson's Disease (2020).