Preprint
Impact of dopamine deficiency and REM sleep behavior disorder on cognition in early neuronal synuclein disease with hyposmia
medRxiv : the preprint server for health sciences
12/13/2024
DOI: 10.1101/2024.12.12.24318917
PMCID: PMC11661337
PMID: 39711699
Abstract
To determine the impact of dopamine deficiency and isolated REM sleep behavior disorder (iRBD) on cognitive performance in early neuronal alpha-synuclein disease (NSD) with hyposmia.
Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) developed by applying regression-based internal norms derived from a robust healthy control (HC) group. Performance was examined for participants with hyposmia classified as NSD-Integrated Staging System (NSD-ISS) Stage 2, either Stage 2A (CSF alpha-synuclein seed amplification assay [SAA]+, SPECT 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 overall 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-value NS; effect size=0.09) and Stage 2B had a statistically worse CSS (z-score mean difference =0.23, p-value <0.05; effect size=0.40) compared with HCs. In Stage 2A participants with hyposmia alone had normal cognition, but presence of comorbid iRBD was associated with significantly worse cognition (z-score mean difference =0.33, p-value <0.05, effect size =0.50). In Stage 2B participants with hyposmia had abnormal cognition (z-score mean difference =0.18, p-value =.0078, effect size =0.29), and superimposed iRBD had a non-statistically significant additive effect.
Using a CSS, early NSD with hyposmia is associated with measurable cognitive deficits compared with robust HCs, particularly in presence of dopamine system impairment or comorbid iRBD, highlighting the importance of focusing on cognition in early-stage synuclein disease.
Details
- Title: Subtitle
- Impact of dopamine deficiency and REM sleep behavior disorder on cognition in early neuronal synuclein disease with hyposmia
- Creators
- Daniel Weintraub - University of PennsylvaniaAnuprita R Nair - University of Iowa, Iowa City, IARyan Kurth - University of Iowa, Iowa City, IAMichael C Brumm - University of IowaMichele K York - Baylor College of MedicineRoseanne 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 Iowa, Iowa City, IAKalpana 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 FoundationTodd Sherer - 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
- Preprint
- Publication Details
- medRxiv : the preprint server for health sciences
- DOI
- 10.1101/2024.12.12.24318917
- PMID
- 39711699
- PMCID
- PMC11661337
- Publisher
- United States
- Language
- English
- Date posted
- 12/13/2024
- Academic Unit
- Biostatistics
- Record Identifier
- 9984759888802771
Metrics
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