Cholinesterase Inhibitor Discontinuation in Patients With Alzheimer’s Disease
Bibliographic record
Abstract
OBJECTIVE: This meta-analysis examined the effects of cholinesterase inhibitor (ChEI) discontinuation in patients with Alzheimer's disease (AD). DATA SOURCES: Electronic records up to March 2014 were searched from MEDLINE, Embase, PsycINFO, Cochrane Library, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature. Search terms included Alzheimer's disease and cholinesterase inhibitors, plus discontinuation or cessation or tapering or withdrawal. There were no language limits. STUDY SELECTION: Randomized, double-blind, placebo-controlled studies investigating the effect of ChEI discontinuation on patients with AD according to standardized criteria (eg, National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association, DSM-IV) and presenting measurable results of neuropsychological testing were included. DATA EXTRACTION: Demographics, setting, ChEI treatment length, discontinuation protocol, follow-up duration, study outcomes, and dropouts during the double-blind phase were extracted. RESULTS: Of 1,430 records returned, 18 were reviewed. Five ChEI discontinuation randomized controlled trials (N = 321 continued and N = 332 discontinued, following patients for 1.5-24 months) were analyzed. Discontinued patients demonstrated a significant worsening of cognition (standard mean Mini-Mental State Examination difference: -0.29 [95% CI, -0.45 to -0.13], N = 300 continued/307 discontinued, P < .001), a significant worsening of neuropsychiatric symptoms (standard mean Neuropsychiatric Inventory difference: -0.32 [-0.51 to -0.12], N = 199/211, P = .001), and significantly higher dropout rates (risk ratio [RR] = 1.33 [1.11-1.59], N = 321/332, P = .002) compared to those who continued. No difference in adverse events was observed (RR = 1.01 [0.85-1.20], N = 314/326, P = .92). CONCLUSIONS: ChEI discontinuation may have negative effects on cognition and neuropsychiatric symptoms, a finding corroborated by a higher incidence of trial dropout.
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 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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".