Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis

Andrew Pearce, Calum Marr, Michaela Dewar, Alan J. Gow

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
64 Downloads (Pure)


Introduction: Possession of one or two e4 alleles of the apolipoprotein E (APOE) gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently.

Method: We conducted a systematic review and meta-analysis of studies which assessed APOE differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo.

Results: Thirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. Post-hoc analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function.

Discussion: Though there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.
Original languageEnglish
Article number815439
JournalFrontiers in Aging Neuroscience
Publication statusPublished - 28 Jan 2022


  • Alzheimer's disease
  • apolipoprotein E
  • brain function
  • brain structure
  • lipid profile
  • meta-analysis
  • physical activity

ASJC Scopus subject areas

  • Ageing
  • Cognitive Neuroscience


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