Selective effects of dopaminergic and noradrenergic degeneration on cognition in Parkinson’s disease
Notice bibliographique
Résumé
Abstract The substantia nigra and locus coeruleus are among the first brain regions to degenerate in Parkinson’s disease. This has important implications for early cognitive deficits as these nuclei are sources of ascending neuromodulators (i.e., dopamine and noradrenaline) that support various cognitive functions like learning, memory, and executive function. However, because most studies of the relationship between patterns of degeneration and cognition have either studied these neuromodulator systems in isolation or studied specific cognitive domains in isolation, it is unknown if degeneration in the substantia nigra and degeneration in the locus coeruleus independently and selectively contribute to different cognitive deficits in Parkinson’s disease. To address this gap, we tested people with Parkinson’s disease and older adults on tasks of positive reinforcement learning, attention/working memory, executive function, and memory to measure performance in domains of cognition specifically thought to be related to dopaminergic and noradrenergic function. Participants also underwent neuromelanin-sensitive magnetic resonance imaging which provides a measure of degeneration of dopamine neurons in the substantia nigra and of noradrenergic neurons in the locus coeruleus. Brain-behaviour relationships were evaluated by separate linear regressions predicting cognitive performance in each domain from substantia nigra and locus coeruleus neuromelanin signal intensities controlling for age, sex, and education. As expected, Parkinson’s disease patients had significantly slower learning from positive feedback and lower performance on tests of attention/working memory, executive function, and memory than controls. Parkinson’s patients also had lower neuromelanin signal intensity in the substantia nigra and locus coeruleus. Examining brain-behaviour relationships, we found that reduced neuromelanin signal in the substantia nigra in Parkinson’s disease patients was independently associated with impaired positive reinforcement learning, controlling for changes in the locus coeruleus, but was not associated with other domains of cognition. In contrast, reduced neuromelanin signal in the locus coeruleus was independently associated with impairments in attention/working memory and executive function, controlling for changes in the substantia nigra, but not with reinforcement learning performance. These results show that substantia nigra degeneration and locus coeruleus degeneration independently and selectively contribute to cognitive deficits and therefore suggests that individual differences in the degree of neurodegeneration in these nuclei could explain the significant heterogeneity that exists in the cognitive and behavioural manifestations of Parkinson’s disease. These findings also highlight the potential value of leveraging known brain-behaviour relationships to develop performance-based measures of cognition that reflect underlying patterns of neurodegeneration.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».