Effectiveness of Donepezil in Reducing Clinical Worsening in Patients with Mild-to-Moderate Alzheimer’s Disease
Bibliographic record
Abstract
BACKGROUND: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer's disease (AD). METHODS: Data from 906 patients (388 receiving placebo; 518 receiving donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10-27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician's Interview-Based Impression of Change plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). RESULTS: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of declining were significantly reduced for donepezil-treated versus placebo patients (p < 0.0001; all definitions). Among patients meeting criteria for clinical worsening, mean declines in MMSE scores were greater for placebo than donepezil-treated patients. CONCLUSION: In this population, donepezil treatment was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared with placebo/untreated patients.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 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".