Language
English
Publication Date
9-1-2025
Journal
Annals of Neurology
DOI
10.1002/ana.27263
PMID
40641332
PMCID
PMC12392052
PubMedCentral® Posted Date
7-11-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Objective: To 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.
Methods: Using 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+).
Results: Participants 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.
Interpretation: Using 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.
Keywords
Humans, Male, Female, REM Sleep Behavior Disorder, Aged, Middle Aged, Synucleinopathies, Dopamine, Cognition, alpha-Synuclein, Cognitive Dysfunction
Published Open-Access
yes
Recommended Citation
Weintraub, Daniel; Nair, Anuprita R; Kurth, Ryan; et al., "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" (2025). Faculty and Staff Publications. 5256.
https://digitalcommons.library.tmc.edu/baylor_docs/5256