Prodromal autonomic symptoms and signs in Parkinson's disease and dementia with Lewy bodies
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Bibliographic record
Abstract
Pathologic staging systems suggest that autonomic dysfunction may be an early manifestation of Parkinson's disease and dementia with Lewy bodies. However, direct evidence is limited, and no prospective studies have measured when autonomic dysfunction starts before disease. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder are at very high risk of developing neurodegenerative synucleinopathy, providing an opportunity to directly observe the development of autonomic dysfunction from prodromal stages of neurodegeneration. Patients with idiopathic REM sleep behavior disorder were followed annually in a prospective cohort that was established in 2004. Urinary, orthostatic, erectile, and constipation symptoms and systolic blood pressure drop from lying to standing were assessed annually. Patients who eventually developed defined synucleinopathy were compared with age-matched controls. The evolution of autonomic measures was assessed with regression analysis to determine when markers first deviated from control values. Sensitivity and specificity of autonomic markers for identification of prodromal disease were calculated. Of 91 patients, 32 developed disease. In prodromal stages, there was substantial autonomic dysfunction observable at least 5 years before diagnosis. On regression analysis, autonomic dysfunction appeared to progress slowly over prodromal periods. The estimated onset of autonomic dysfunction ranged from 11 years to 20 years, and systolic drop (20.4 years) and constipation (15.3 years) had the earliest estimates. Systolic drop, erectile dysfunction, and constipation could identify disease up to 5 years before diagnosis with sensitivity ranging from 50% to 90%. By directly observing development of neurodegenerative synucleinopathy, we confirmed that autonomic dysfunction can occur early in neurodegenerative synucleinopathy, even as long as 20 years before defined disease. © 2013 Movement Disorder Society.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it