Evidence map›Paper›PMID 27911294›Full record

ArticleJournal of Alzheimer's disease : JAD2017

Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment.

Sophie Sokolow, Xiaohui Li, Lucia Chen, Kent D Taylor, Jerome I Rotter, Robert A Rissman, Paul S Aisen, Liana G Apostolova

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.8field-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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Emerging significance of butyrylcholinesterase.World journal of experimental medicine · 2024
    Review
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  11. Exploring the Chemical Profiles and Biological Values of TwoAntioxidants (Basel, Switzerland) · 2021
    Article
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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

8 authors at 6 institutions in 1 country.

Sophie SokolowSchool of Nursing, University of California at Los Angeles, Los Angeles, CA, USA.
Xiaohui LiInstitute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Lucia ChenSchool of Nursing, University of California at Los Angeles, Los Angeles, CA, USA.
Kent D TaylorInstitute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Robert A RissmanAlzheimer's Disease Cooperative Study, University of California San Diego, San Diego, CA, USA.
Paul S AisenAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
Liana G ApostolovaIndiana University School of Medicine, Indiana Alzheimer's Disease Center, Indianapolis, IN, USA.
Harbor–UCLA Medical Center · USUniversity of California, Los Angeles · USIndiana University School of MedicineUCLA Medical Center · USUniversity of California, San Diego · USUniversity of Southern California · US

Funding

TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
UCLA ALZHEIMERS DISEASE RESEARCH CENTERP50AG016570 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BREDESEN, DALE E. · 1999 to 2014
$25.9M
Imaging and genetic biomarkers for Alzheimer's diseaseR01AG040770 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI APOSTOLOVA, LIANA G · 2012 to 2016
$1.4M
Pharmacogenetics of donepezil in mild cognitively impaired patientsK23AG051416 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SOKOLOW, SOPHIE · 2015 to 2017
$520k
Imaging epigenetics of Alzheimer's DiseaseK02AG048240 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI APOSTOLOVA, LIANA G · 2014 to 2016
$434k
NCATS NIH HHS UL1 TR000124NIA NIH HHS K02 AG048240NIA NIH HHS K23 AG051416NIA NIH HHS P30 AG010133NIA NIH HHS P50 AG016570NIA NIH HHS R01 AG040770NIA NIH HHS U01 AG010483
6 · The paper itself

Abstract

backgroundDonepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results.

objectivesTo determine whether BChE-K genotype predicts response to donepezil in MCI.

methodsWe examined the association between BChE-K genotype and changes in cognitive function using the data collected during the ADCS vitamin E/donepezil clinical trial in MCI.

resultsWe found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in MMSE and CDR-SB scores compared to the common allele in MCI subjects treated during the 3-year trial. We found faster MMSE decline and CDR-SB rise in BChE-K homozygous individuals treated with donepezil compared to the untreated. We observed similar interactions between BChE-K genotype and steeper changes in MMSE and CDR-SB scores in APOE4 carriers treated with donepezil compared to controls.

conclusionBChE-K polymorphisms are associated with deleterious changes in cognitive decline in MCI patients treated with donepezil for 3 years. This indicates that BChE-K genotyping should be performed to help identify subsets of subjects at risk for donepezil therapy, like those carrying APOE4. BChE-K and APOE4 carriers should not be prescribed off-label donepezil therapy for MCI management.

Indexed as

AgedAged, 80 and overApolipoprotein E4ButyrylcholinesteraseCholinesterase InhibitorsCognitive DysfunctionDisease ProgressionDonepezilFemaleGene FrequencyGenotypeHumansIndansLongitudinal StudiesMaleMental Status ScheduleApolipoprotein E4ButyrylcholinesteraseCholinesterase InhibitorsDonepezilIndansPiperidinesAlzheimer’s diseasebutyrylcholinesteraseclinical trialdonepezilmild cognitive impairmentpharmacogeneticstherapeutics

Identifiers

PMID27911294
PMCPMC5534361
OpenAlexW2558594237

What OpenQuestion holds

Textmetadata
LicenceTDM
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.