Association of Concurrent Olfactory Dysfunction and Probable Rapid Eye Movement Sleep Behavior Disorder with Early Parkinson's Disease Progression
Bibliographic record
Abstract
ABSTRACT Background Parkinson's disease (PD), with either rapid eye movement sleep behavior disorder (RBD) or olfactory dysfunction (OD), has been associated with disease progression. However, there is currently heterogeneity in predicting prognosis. Objectives To identify whether the concurrent presence of OD and probable RBD (pRBD) in PD (Dual hit in PD, PD‐DH) is associated with disease progression. Methods We included 420 patients with de novo PD from the Parkinson's Progression Markers Initiative: 180 PD only (PD), 82 PD with OD (PD‐OD), 94 PD with pRBD (PD‐pRBD), and 64 PD with both OD and pRBD (PD‐DH). Participants underwent motor and nonmotor evaluations, dopamine transporter imaging, and cerebrospinal fluid (CSF) assessment. Data were analyzed with generalized estimating equations and Cox proportional hazards analysis. Results The PD‐DH subtype was associated with higher scores and faster progression rates in Movement Disorder Society–Unified PD Rating Scale (MDS‐UPDRS) Parts II and III. Also, patients in PD‐DH group had faster deterioration in nonmotor symptoms, including MDS‐UPDRS Part I score, Montreal Cognitive Assessment, Hopkins Verbal Learning Test–Revised, Wechsler Memory Scale‐Third edition (WMS‐III) Letter Number Sequencing score, Symbol Digit Modalities Test, and Scales for Outcomes in PD–Autonomic scores, with all P values <0.002. Moreover, the PD‐DH subtype had a higher mild cognitive impairment risk (hazard ratio = 1.756, 95% confidence interval [CI] = 1.132–2.722; P = 0.012), faster decline in caudate standard uptake values (β = −0.03, 95% CI = −0.06 to −0.008, P = 0.012), and CSF α‐synuclein levels (β = −77, 95% CI = −149 to −5, P = 0.034) than the PD group. Conclusion Coexisting pRBD and OD in patients with PD may be associated with faster progressions in motor measurements and in cognitive and autonomic symptoms, indicating PD‐DH as a more aggressive subtype for PD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".