Evidence map›Paper›PMID 28065843›Full record

SynthesisProgress in neuro-psychopharmacology & biological psychiatry2017

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies.

Alan S Lewis, Gerrit I van Schalkwyk, Michael H Bloch

Abstract readMeta-AnalysisReview
In one paragraph

Synthesis in Progress in neuro-psychopharmacology & biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.

  1. Pooled it
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  12. The controversial effect of smoking and nicotine in SARS-CoV-2 infection.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023
    Review
  13. Neuropharmacological Potential of Diterpenoid Alkaloids.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  14. Article
  15. Article
  16. European Psychiatric Association guidance on treatment of cognitive impairment in schizophrenia.European psychiatry : the journal of the Association of European Psychiatrists · 2022
    Review
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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

3 authors at 1 institution in 1 country.

Alan S LewisDepartment of Psychiatry, Yale University, 34 Park Street, 3rd Floor, Research, New Haven, CT 06508, United States. Electronic address: alan.lewis@yale.edu.
Gerrit I van SchalkwykYale Child Study Center, 230 S. Frontage Road, New Haven, CT 06520, United States.
Michael H BlochYale Child Study Center, 230 S. Frontage Road, New Haven, CT 06520, United States.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
RESEARCH TRAINING - BIOLOGICAL SCIENCEST32MH014276 · NIMH · YALE UNIVERSITY · PI Marina R Picciotto · 1985 to 2026
$7.2M
Research Training for Medical Students & Physician-Scientists in Child PsychiatryR25MH077823 · NIMH · YALE UNIVERSITY · PI ANDRES S MARTIN · 2006 to 2026
$4.0M
NCATS NIH HHS UL1 TR001863NIMH NIH HHS R25 MH077823NIMH NIH HHS T32 MH014276
6 · The paper itself

Abstract

Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer's disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen's d=-0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d=-1.18 to - 0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR.

Indexed as

alpha7 Nicotinic Acetylcholine ReceptorAnimalsCognition DisordersHumansMental DisordersNicotinic AgonistsPubMedRodentiaalpha7 Nicotinic Acetylcholine ReceptorNicotinic AgonistsAlpha7 nicotinic receptorAlzheimer's diseaseClinical trialCognitionMeta-analysisSchizophrenia

Identifiers

PMID28065843
PMCPMC5446073
OpenAlexW2570756641

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.