Bibliographic record
Abstract
OBJECTIVE: To systematically review published clinical trials of the pharmacotherapy of Alzheimer disease (AD). METHOD: We searched MEDLINE for published English-language medical literature, using Alzheimer disease and treatment as key words. No other search engine was used. Our review focused on randomized clinical trials (RCTs) and corresponding metaanalyses. RESULTS: Although there are many RCTs for the treatment of mild cognitive impairment (MCI), none have been successful in their primary analysis. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in 3- to 12-month placebo-controlled RCTs assessing cognitive, functional, behavioural, and global outcomes in patients with mildly to moderately severe AD. Recent data from patients with severe stages of AD demonstrate the efficacy of donepezil on cognitive and functional measures but not on behaviour. The N-methyl-D-aspartate receptor antagonist memantine has been demonstrated to be effective in 6-month, placebo-controlled RCTs of 6 months duration assessing cognitive, functional, and global outcomes of inpatients with moderate-to-severe AD (defined as a Mini Mental State Examination score below 20). Post hoc analyses have demonstrated a benefit in regard to agitation and (or) aggression, but this needs to be confirmed in a prospective RCT across Canada. Disease-modifying treatments are being tested in mild stages of AD in 18-month RCTs with cognitive and global outcomes as primary efficacy outcomes, primarily with drugs reducing amyloid synthesis or aggregation. Successful treatment in mild stages of AD could lead to RCTs in MCI and, possibly, in genetically high-risk asymptomatic individuals. CONCLUSION: The significant advances in the symptomatic pharmacotherapy of AD may be followed by disease-modification treatments.
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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 | 0.008 | 0.026 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.003 |
| Bibliometrics | 0.009 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 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".