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Record W4405397817 · doi:10.1101/2024.12.12.24318917

Impact of dopamine deficiency and REM sleep behavior disorder on cognition in early neuronal synuclein disease with hyposmia

2024· preprint· en· W4405397817 on OpenAlexaboutno aff
Daniel Weintraub, Ryan Kurth, Michael C. Brumm, Michele K. York, Roseanne D. Dobkin, Kenneth Marek, Caroline M. Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M. Chahine, Christopher S. Coffey, Kalpana Merchant, Kathleen L. Poston, Tatiana Foroud, Brit Mollenhauer, Ethan Brown, Karl Kieburtz, Mark Frasier, Todd Sherer, Sohini Chowdhury, Roy N. Alcalay, Aleksandar Videnović

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsnot available
FundersJanssen PharmaceuticalsOffice of Rural HealthSpark TherapeuticsParkinsonfondenNational Institutes of HealthH. Lundbeck A/SServierDeutsche ForschungsgemeinschaftProthenaAcorda TherapeuticsBiogenInternational Parkinson and Movement Disorder SocietyDemensförbundetNorthwestern UniversityParkinson's FoundationGenentechUniversity of PittsburghEli Lilly and CompanyNational Institute of Neurological Disorders and StrokeMassachusetts General HospitalU.S. Department of DefenseSanofiMichael J. Fox Foundation for Parkinson's Research
KeywordsHyposmiaREM sleep behavior disorderCognitionDopamine transporterInternal medicineParkinson's diseaseCognitive declineStage (stratigraphy)PsychologyAudiologyGastroenterologyDopamineMedicineDiseasePsychiatryDementiaDopaminergicBiology

Abstract

fetched live from OpenAlex

Objectives: 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. Methods: 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+). Results: 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. Interpretation: 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.279
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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