Evolution of prodromal clinical markers of Parkinson disease in a GBA mutation-positive cohort.
Notice bibliographique
Résumé
Importance. Numerically, the most important genetic risk factor for the development of Parkinson disease (PD) is the presence of a glucocerebrosidase gene (GBA) mutation. \n \nObjective. To evaluate longitudinally and clinically a GBA mutation–positive cohort and the evolution of the prodromal features of PD. \n \nDesign, Setting, and Participants. Participants in a study of the etiology and prodrome of PD were reevaluated in this clinic-based 2-year follow-up report. Patients with type 1 Gaucher disease (GD) and heterozygous GBA mutation carriers were recruited in 2010 from the Lysosomal Storage Disorder Unit at the Royal Free Hospital, London, England. Thirty patients who previously received a diagnosis of type 1 GD, 28 heterozygous GBA mutation carriers, and 26 genetically unrelated controls were included. Exclusion criteria included a diagnosis of PD or dementia for both the patients with GD and the GBA mutation carriers and any existing neurological disease for the controls. \n \nMain Outcomes and Measures. Assessment was performed for clinical markers using standardized scales for hyposmia, rapid eye movement sleep behavior disorder, depression, autonomic dysfunction, cognitive function, and parkinsonian motor signs (using the Unified Parkinson’s Disease Rating Scale motor subscale [UPDRS part III]). \n \nResults. Over 2 years, depression scores were significantly worse for heterozygous carriers (mean baseline, 0.65; mean follow-up, 2.88; P = .01), rapid eye movement sleep behavior disorder scores were significantly worse for patients with GD (mean baseline, 0.93; mean follow-up, 2.93; P < .001) and heterozygotes (mean baseline, 0.10; mean follow-up, 2.30; P < .001), and UPDRS part III scores were significantly worse for patients with GD (mean baseline, 4.29; mean follow-up, 7.82; P < .001) and heterozygotes (mean baseline, 1.97; mean follow-up, 4.50; P < .001). For controls, there was a small but significant deterioration in the UPDRS part II (activities of daily living) score (mean baseline, 0.00; mean follow-up, 0.58; P = .006). At 2 years, olfactory and cognitive assessment scores were lower in patients with GD and heterozygotes compared with controls, but they did not differ significantly from baseline. When the results from the patients with GD and the heterozygotes were combined, a significant deterioration from baseline was observed, as reflected in the Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (mean baseline, 0.51; mean follow-up, 2.63; P < .001), Beck Depression Inventory (mean baseline, 1.72; mean follow-up, 4.44; P = .002), and UPDRS part II (mean baseline, 0.88; mean follow-up, 2.01; P < .001) and part III scores (mean baseline, 3.09; mean follow-up, 6.10; P < .001) (all P < .01), and at 2 years, significant differences in University of Pennsylvania Smell Identification Test, Unified Multiple System Atrophy Rating Scale, Mini-Mental State Examination, Montreal Cognitive Assessment, and UPDRS part II and part III scores were observed between patients with GD/heterozygotes and controls (all P < .05). \n \nConclusions and Relevance. This study indicates that, as a group, GBA mutation–positive individuals show a deterioration in clinical markers consistent with the prodrome of PD. Within this group of individual, 10% appear to be evolving at a more rapid rate.
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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 | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».