Evidence map›Paper›PMID 30646339›Full record

SynthesisJAMA network open2018

Association of Concomitant Use of Cholinesterase Inhibitors or Memantine With Cognitive Decline in Alzheimer Clinical Trials: A Meta-analysis.

Richard E Kennedy, Gary R Cutter, Mackenzie E Fowler, Lon S Schneider

Open access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in JAMA network open, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Observational
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Observational
  11. Article
  12. Review
  13. Article
  14. Observational
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Richard E KennedyUniversity of Alabama at Birmingham, Birmingham.
Gary R CutterUniversity of Alabama at Birmingham, Birmingham.
Mackenzie E FowlerUniversity of Alabama at Birmingham, Birmingham.
Lon S SchneiderKeck School of Medicine, University of Southern California, Los Angeles.
University of Alabama at Birmingham · USUniversity of Southern California · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
In Silico Screening of Medications for Slowing Alzheimer's Disease Progression.R01AG057684 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KENNEDY, RICHARD E, SCHNEIDER, LON S · 2017 to 2021
$3.2M
Synthesis of Longer-Term Alzheimer Disease Studies in Order to Model and ImproveR01AG037561 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SCHNEIDER, LON S · 2011 to 2013
$1.6M
NIA NIH HHS R01 AG037561NIA NIH HHS R01 AG057684NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

Importance: Clinical trials in Alzheimer disease (AD) generally allow participants to continue receiving concomitant medications, including cholinesterase inhibitors (ChEIs) and memantine, if the dose is stable. Previous analysis of observational studies indicates such individuals experience greater rate of decline on cognitive testing than those not receiving such medications. Objective: To investigate whether concomitant use of ChEIs or memantine is associated with cognitive outcomes in AD clinical trials. Data Sources: Meta-database of 18 studies from the Alzheimer Disease Cooperative Study and Alzheimer Disease Neuroimaging Initiative. Study Selection: All studies with data on ChEI and memantine use that included assessment of specified outcome measures. Data Extraction and Synthesis: The analysis estimated annual rate of decline on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) using linear mixed-effects models, and compared rates for participants receiving ChEIs and memantine, alone and combined, with participants not receiving either medication using random-effects meta-analysis. Main Outcomes and Measures: Annual rate of change on the ADAS-cog. Results: Across 10 studies, of 2714 participants, the mean (SD) age was 75.0 (8.2) years, 58% were female, and 9% were racial/ethnic minorities. There were 906 participants (33.4%) receiving ChEIs, 143 (5.3%) receiving memantine, 923 (34.0%) receiving both, and 742 (27.3%) receiving neither. Meta-analysis showed those receiving ChEIs or memantine were associated with significantly greater annual rate of decline on the ADAS-cog than those receiving neither medication (1.4 points/y; 95% CI, 0.1-2.7). Conclusions and Relevance: Similar to observational studies, many participants in AD clinical trials receiving ChEIs or memantine experience greater cognitive decline. This difference is nearly as large as the hypothesized effect sizes of the treatments investigated in the trials. Concomitant use of ChEIs or memantine may be confounded with outcomes on the ADAS-cog and should be considered in design of clinical trials of potential therapeutic agents for AD. Post hoc analyses stratifying by ChEIs or memantine must be interpreted cautiously given the potential for confounding.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseCholinesterase InhibitorsCognitive DysfunctionDopamine AgentsDrug Therapy, CombinationExcitatory Amino Acid AntagonistsFemaleHumansMaleMemantineNeuropsychological TestsCholinesterase InhibitorsDopamine AgentsExcitatory Amino Acid AntagonistsMemantine

Identifiers

PMID30646339
PMCPMC6324361
OpenAlexW2900332872

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.