Evidence map›Paper›PMID 39828710›Full record

SynthesisTrials2025

The effect of the APOE4 genotype on physiological and cognitive health in randomised controlled trials with an exercise intervention: a systematic review and meta-analysis.

Felicity S E Spencer, Richard J Elsworthy, Leigh Breen, Jon R B Bishop, Connor Dunleavy, Sarah Aldred

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Trials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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

6 authors.

Felicity S E SpencerSchool of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK. fss220@student.bham.ac.uk.ORCID http://orcid.org/0009-0002-3063-8147
Richard J ElsworthySchool of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Leigh BreenSchool of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Jon R B BishopBirmingham Clinical Trials Unit, Institute of Applied Health Research, Public Health Building, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Connor DunleavySchool of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Sarah AldredSchool of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK. s.aldred.1@bham.ac.uk.

Funding

MRC-NIHR Trials Methodology Research Partnership (TMRP) MR/W006049/1
6 · The paper itself

Abstract

backgroundAlzheimer's disease is caused by modifiable and non-modifiable risk factors. Randomised controlled trials have investigated whether the strongest genetic risk factor for Alzheimer's disease, APOE4, impacts the effectiveness of exercise on health. Systematic reviews are yet to evaluate the effect of exercise on physical and cognitive outcomes in APOE genotyped participants. A quality assessment of these randomised controlled trials is needed to understand the impact genotype has on the potential success of intervention. This systematic review aimed to determine if the APOE4 genotype influences the effectiveness of exercise-based randomised controlled trials.

methodSearches on MEDLINE, EMBASE, and PsycINFO identified eligible exercise based randomised controlled trials incorporating participants with varied cognitive abilities. Quality assessments were conducted.

resultsNineteen studies met the inclusion criteria for systematic review, and 3 for the meta-analysis. Very low to moderate quality evidence showed that APOE4 carriers benefitted more than APOE4 non-carriers on cognitive (e.g. executive function, learning) and physical (e.g. relative telomere length) outcomes after exercise; and that APOE4 non-carriers benefited over carriers for physical (serum BDNF, gait speed) and cognitive (global cognition, verbal memory) markers. Very low quality evidence indicated that there was no evidence of difference between APOE4 carriers and non-carriers on physical function outcomes in meta-analysis. Several areas of study design and reporting, including maintenance of relative exercise intensity and complete statistical reporting, were identified as needing improvement. DISCUSSION: This systematic review found very limited evidence to suggest that exercise interventions can benefit APOE4 carriers and non-carriers equally, though conclusions were limited by evidence quality. Further randomised controlled trials, stratifying participants by APOE status are required to better understand the relationship between APOE genotype and the effect of exercise on health-related outcomes.

trial registrationThis review was registered with PROSPERO (CRD42023436842). Registered on June 16, 2023.

Indexed as

Alzheimer DiseaseApolipoprotein E4CognitionExerciseExercise TherapyAgedBrain-Derived Neurotrophic FactorFemaleGenotypeHumansMaleRandomized Controlled Trials as TopicTreatment OutcomeApolipoprotein E4Brain-Derived Neurotrophic FactorAlzheimer’s diseaseExerciseRandomised controlled trials

Identifiers

PMID39828710
PMCPMC11744846

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Registered trials

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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.