Journal article
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
Annals of neurology, Vol.98(3), pp.482-491
09/2025
DOI: 10.1002/ana.27263
PMCID: PMC12392052
PMID: 40641332
Abstract
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.
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+).
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.
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. ANN NEUROL 2025.
Details
- Title: Subtitle
- 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
- Creators
- Daniel Weintraub - University of PennsylvaniaAnuprita R Nair - University of IowaRyan Kurth - University of IowaMichael C Brumm - University of IowaChristine Kohnen - Department of Biostatistics, University of Iowa, Iowa City, IAMichele K York - Baylor College of MedicineRoseanne D Dobkin - Rutgers, The State University of New JerseyKenneth Marek - Institute for Neurodegenerative DisordersCaroline Tanner - University of California, San FranciscoTanya Simuni - Northwestern UniversityAndrew Siderowf - University of PennsylvaniaDouglas Galasko - University of California San DiegoLana M Chahine - University of PittsburghChristopher Coffey - University of IowaKalpana Merchant - Northwestern UniversityKathleen L Poston - Stanford UniversityTatiana Foroud - Indiana University IndianapolisBrit Mollenhauer - Paracelsus Elena Klinik KasselEthan G Brown - University of California, San FranciscoKarl Kieburtz - University of RochesterMark Frasier - Michael J. Fox FoundationSohini Chowdhury - Michael J. Fox FoundationRoy N Alcalay - Tel Aviv Sourasky Medical CenterAleksandar Videnovic - Massachusetts General HospitalParkinson's Progression Markers Initiative
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.98(3), pp.482-491
- DOI
- 10.1002/ana.27263
- PMID
- 40641332
- PMCID
- PMC12392052
- NLM abbreviation
- Ann Neurol
- ISSN
- 1531-8249
- eISSN
- 1531-8249
- Publisher
- WILEY
- Grant note
- Michael J. Fox Foundation for Parkinson's Research
- Language
- English
- Electronic publication date
- 07/11/2025
- Date published
- 09/2025
- Academic Unit
- Biostatistics
- Record Identifier
- 9984845654802771
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