ArticleNeurobiology of disease2023
Levodopa responsive freezing of gait is associated with reduced norepinephrine transporter binding in Parkinson's disease.
Article in Neurobiology of disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- Freezing of Gait Levodopa Response Pattern in Parkinson's Disease Provides Clues to Pathophysiology.The European journal of neuroscience · 2026Review
- Pharmacologically Modulating the Noradrenergic Arousal System to Reduce Freezing of Gait in Parkinson's Disease: Study Protocol of the International AnTi-FREEZE Study.The European journal of neuroscience · 2026Article
- The Noradrenergic Brain in Parkinson's Disease.Current neurology and neuroscience reports · 2026Review
- Mapping the Silent Onset of Parkinson's Disease: Monoamine Imaging in the Era of the Race for Preclinical Intervention.Current neurology and neuroscience reports · 2026Review
- Neurotransmitter Systems Underlying Freezing of Gait (FOG) in Parkinson's Disease.The European journal of neuroscience · 2026Review
- Aberrant Beta-Band Network Alteration Preceding Freezing of Gait in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- What is new in Freezing of Gait?Journal of neurology · 2026Review
- Self-delivered arousal-heightening stimuli to improve mobility in persons with parkinsonism: A case series.Journal of Parkinson's disease · 2026Article
- Neuroimaging and Pathology Biomarkers in Parkinson's Disease and Parkinsonism.Brain sciences · 2026Article
- Explainable SHAP- XGBoost with DAT and clinical data for freezing of gait detection in Parkinson disease.NPJ Parkinson's disease · 2026Article
- Neural signatures of turn-induced freezing of gait in Parkinson's disease: insights from phase-specific cortico-subthalamic dynamics.NPJ Parkinson's disease · 2025Article
- Management of freezing of gait - mechanism-based practical recommendations.Nature reviews. Neurology · 2025Review
- A possible pathway to freezing of gait in Parkinson's disease.Journal of Parkinson's disease · 2025Article
- Technology for measuring freezing of gait: Current state of the art and recommendations.Journal of Parkinson's disease · 2025Review
- Impact of excessive daytime sleepiness on the progression of freezing of gait in de novo Parkinson's disease: a cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Noradrenergic cardiac denervation is associated with gait velocity in Parkinson disease: a dual ligand PET study.European journal of nuclear medicine and molecular imaging · 2024Article
- Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design.Movement disorders : official journal of the Movement Disorder Society · 2023Observational
- Neuromelanin-sensitive MRI correlates of cognitive and motor function in Parkinson's disease with freezing of gait.Frontiers in dementia · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFreezing of gait (FOG) is a major cause of falling in Parkinson's disease (PD) and can be responsive or unresponsive to levodopa. Pathophysiology is poorly understood.
objectiveTo examine the link between noradrenergic systems, the development of FOG in PD and its responsiveness to levodopa.
methodsWe examined norepinephrine transporter (NET) binding via brain positron emission tomography (PET) to evaluate changes in NET density associated with FOG using the high affinity selective NET antagonist radioligand [
resultsLinear mixed models identified significant reductions in whole brain NET binding in the OFF-FOG group compared to the NO-FOG group (-16.8%, P = 0.021) and regionally in the frontal lobe, left and right thalamus, temporal lobe, and locus coeruleus, with the strongest effect in right thalamus (P = 0.038). Additional regions examined in a post hoc secondary analysis including the left and right amygdalae confirmed the contrast between OFF-FOG and NO-FOG (P = 0.003). A linear regression analysis identified an association between reduced NET binding in the right thalamus and more severe New FOG Questionnaire (N-FOG-Q) score only in the OFF-FOG group (P = 0.022).
conclusionThis is the first study to examine brain noradrenergic innervation using NET-PET in PD patients with and without FOG. Based on the normal regional distribution of noradrenergic innervation and pathological studies in the thalamus of PD patients, the implications of our findings suggest that noradrenergic limbic pathways may play a key role in OFF-FOG in PD. This finding could have implications for clinical subtyping of FOG as well as development of therapies.
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