Exploring the Distinct Effect of Age at Onset and Caudate Denervation on Cognitive Deficits in Early Parkinson’s Disease
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Bibliographic record
Abstract
Older age at onset and baseline caudate dopaminergic denervation are recognized risk factors for cognitive impairment in Parkinson’s disease (PD), posing challenges in identifying their relative contribution to cognitive outcomes. The objective of this study was to assess the distinct contribution of age at onset and baseline caudate dopaminergic binding to the early cognitive deficits in PD patients. We examined the relationship between baseline dopaminergic striatal dysfunction (measured using [<sup>123</sup>I]-FP-CIT SPECT), age at disease onset and neuropsychological performance in 128 <i>drug-naive</i> PD patients, utilizing putaminal and caudate binding values of 77 healthy controls (HC) for a comparative exploration of age-dependent loss of DAT availability. Additionally, we investigated whether age at onset and DAT binding value of the caudate could independently predict cognitive changes over a median of 7-year follow-up. [<sup>123</sup>I]-FP-CIT-SPECT binding values had a significant negative correlation with age in both PD and HC, but in PD, aging was linked with a steeper slope for the caudate than the putamen. Older age at onset and lower caudate uptake were associated with worse global cognitive function and performance in specific neuropsychological tests at baseline and demonstrated to be significant independent predictors of cognitive dysfunction at follow-up. Our findings confirm a differential age effect on [<sup>123</sup>I]-FP-CIT binding in the striatal subregions of <i>de novo</i> PD patients. Notably, we found less age-related attrition of dopaminergic binding in the putamen than in the caudate, reflecting likely the superimposition of putaminal compensatory mechanisms and an increased predisposition of old onset PD patients to develop cognitive disturbances.
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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