Apathy in Dementia Methylphenidate Trial 2 (ADMET2): Results of a phase III, placebo‐controlled, double‐blind, 6‐month, multi‐center, randomized clinical trial
Bibliographic record
Abstract
Abstract Background Apathy is one of the most common and debilitating neuropsychiatric symptoms of Alzheimer’s Disease (AD). Two previous trials that suggested methylphenidate was safe and efficacious involved only 60 participants each, followed for 6 weeks. A larger, longer‐lasting trial was required to confirm those promising findings. Methods ADMET 2 was a phase III, placebo‐controlled, 6‐month, multi‐center, randomized (1:1, 20 mg methylphenidate per day or placebo) clinical trial that randomized 200 participants with AD and apathy. Primary outcomes included: (1) the mean difference on the Neuropsychiatric Inventory Apathy (NPI‐A) subscale scores measured as change from baseline to 6 months, and/or (2) the odds of a rating of improvement on the modified AD Cooperative Study Clinical Global Impression of Change (ADCS‐CGIC) at month 6 compared with baseline. Secondary outcomes included change in cognition, safety, and cost‐effectiveness measured monthly for up to 6 months. Results 200 individuals were randomized (65.8% were males; 34.2% were females; avg age=76 years; 75.3% had some college education or greater; mean Mini‐Mental State Examination score at baseline was 18.9). There was a larger difference in the methylphenidate group compared with the placebo group in NPI‐A score from baseline to 6 months using a mixed model (Mean difference = ‐1.25; 95% CI: ‐2.03, ‐0.47, p = 0.002) with the largest change observed during the first two months. At 6 months, the ADCS‐CGIC showed that 43.8% (39/89) of participants in the methylphenidate group improved compared with 35.2% (32/91) of study participants in the placebo group (odds ratio 1.90 (95% CI: 0.95, 3.84), favoring methylphenidate, but not reaching statistical significance (p = 0.071)). There were no significant differences in other assessments. The safety profile was similar between the two groups. Conclusion ADMET 2 showed a small to medium benefit for methylphenidate in the treatment of apathy in AD. The effect was observed at 2 months and was sustained throughout the 6 months of the study. Adverse events were mild. These results support previous observations in smaller studies. Methylphenidate offers a viable treatment for patients suffering from apathy in AD.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".