ArticleMovement disorders : official journal of the Movement Disorder Society2025
Selective Effects of Substantia Nigra and Locus Coeruleus Degeneration on Cognition in Parkinson's Disease.
Article in Movement disorders : official journal of the Movement Disorder Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Locus Coeruleus as a Master Regulator of Diverse Functions in the Central Nervous System: Its Relevance in Ageing and Neurodegenerative Disorders.Annals of neurosciences · 2026Review
- Locus coeruleus α-synuclein overexpression induces prodromal Parkinsonian features in mice.NPJ Parkinson's disease · 2026Article
- Neuroimaging and Pathology Biomarkers in Parkinson's Disease and Parkinsonism.Brain sciences · 2026Article
- Research progress on the role of the locus coeruleus in cognitive function.Frontiers in human neuroscience · 2026Review
- Parkinson's disease physiopathology-beyond theFrontiers in aging neuroscience · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
backgroundThe substantia nigra (SN) and locus coeruleus (LC) are among the first brain regions to degenerate in Parkinson's disease (PD). This has important implications for early cognitive deficits because these nuclei are sources of ascending neuromodulators (i.e., dopamine and noradrenaline) that support various cognitive functions such as learning, memory, and executive function.
objectiveOur aim was to investigate the selective and independent contributions of SN and LC degeneration to cognitive deficits in PD.
methodsWe ran a cross-sectional study testing patients with PD and older adults on tasks of positive reinforcement learning, attention/working memory, executive function, and memory to measure cognitive performance in domains thought to be related to dopaminergic and noradrenergic function. Participants also underwent neuromelanin-sensitive magnetic resonance imaging as a measure of degeneration.
resultsReduced SN neuromelanin signal in PD was independently associated with impaired positive reinforcement learning (β = 0.41, 95% confidence interval [CI]: 0.08, 0.74) controlling for changes in the LC. In contrast, reduced LC neuromelanin signal was independently associated with impairments in attention/working memory (β = 0.20, 95% CI [-0.47, -0.10]) and executive function (β = 0.22, 95% CI: -0.57, -0.24), controlling for changes in the SN.
conclusionsThese results suggest that SN and LC degeneration may contribute to different cognitive deficits, potentially explaining the heterogeneity that exists in the cognitive manifestations of PD. These results also highlight the potential value of leveraging brain-behavior relationships to develop performance-based measures of cognition that could be used to characterize the phenotypic differences associated with underlying patterns of neurodegeneration. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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