ArticleAnnals of neurology2025
Cognitive Performance in Early Neuronal Synuclein Disease with Hyposmia but without Motor Disability: Association with Dopamine Deficiency and Isolated Rapid Eye Movement Sleep Behavior Disorder.
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Subjective Cognitive Concerns and Cognitive Trajectories in Parkinson's Disease: Biomarker Impact.Annals of clinical and translational neurology · 2026Article
- Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy.Annals of clinical and translational neurology · 2026Article
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Abstract
objectiveTo determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.
methodsUsing Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).
resultsParticipants were stage 2A (n = 101), stage 2B (N = 227), and HCs (n = 158). Although stage 2 had intact Montreal Cognitive Assessment scores (mean [SD] = 27.0 [2.3]), stage 2A had a numerically worse CSS (z-score mean difference = 0.05, p = NS; effect size = 0.09) and stage 2B a statistically worse CSS (z-score mean difference = 0.23, p < 0.05; effect size = 0.40) compared with HCs. In stage 2A, hyposmia alone was associated with normal cognition, but those with comorbid iRBD had significantly worse cognition (z-score mean difference = 0.33, p < 0.05, effect size =0.50). In stage 2B, hyposmia alone had abnormal cognition (z-score mean difference = 0.18, p = 0.0078, effect size = 0.29), and superimposed iRBD had a statistically significant additive effect.
interpretationUsing a novel CSS, we demonstrated that hyposmia is associated with cognitive deficits in prodromal NSD without motor disability, particularly when comorbid dopamine system impairment or comorbid iRBD is present. Therefore, it is critical to include and assess cognition at all stages when studying synuclein disease, even in the absence of motor disability. ANN NEUROL 2025;98:482-491.
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