DOI: 10.1002/alz.080474 ISSN: 1552-5260

Aerobic exercise and volumetric change in the human hippocampus: A meta‐analysis of randomized controlled trials in healthy older individuals

Guilherme Moraes Balbim, Nárlon Cássio Boa Sorte Silva, Lisanne F Ten Brinke, Ryan S Falck, Tibor Hortobágyi, Urs Granacher, Kirk I. Erickson, Rebeca Hernández‐Gamboa, Teresa Liu‐Ambrose
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



There is promising, albeit equivocal, evidence that aerobic exercise training (AET) increases human hippocampal volume. The evidence is unclear, as recent randomized controlled trials (RCTs) have failed to replicate AET’s previously reported favorable effects on hippocampal volume in cognitively unimpaired older individuals. We thus conducted a meta‐analysis of RCTs investigating the effects of AET on hippocampal volume and cardiorespiratory fitness (CRF) in cognitively unimpaired, healthy older individuals.


A meta‐analysis of RCTs that delivered AET interventions to older individuals. Inclusion criteria were: 1) cognitively unimpaired, healthy individuals aged ≥ 50; 2) AET intervention delivered for at least four weeks; 3) at least one intervention group and one control group; 4) reported data of the effects of AET on hippocampal volume. Two authors independently screened titles, abstracts, and full texts, performed data extraction and methodological quality assessment of included studies. We performed meta‐analyses with random‐effects robust variance estimation models and meta‐regression analyses to test associations between changes in CRF and hippocampal volume. The primary outcome was changes in hippocampal volume, and the secondary outcome was changes in CRF.


Eight parent trials and one secondary outcome article were eligible. The meta‐analytic summary of 17 effect sizes indicated no significant effects of AET on hippocampal volume (SMD = 0.10, 95%CI ‐0.01 to 0.21, p = 0.073). Meta‐analysis of nine studies and effect sizes showed that AET moderately improved cardiorespiratory fitness (SMD = 0.30, 95%CI 0.12 to 0.48, p = 0.005). Improvement in CRF was not statistically associated with changes in hippocampal volume (bSE = 0.05, SE = 0.51, p = 0.923). Methodological quality was poor in one, fair in three, good in four, and excellent in one trial.


AET did not show robust effects on hippocampal volume in cognitively unimpaired, healthy older individuals. Since AET significantly improved CRF, a lack of training fidelity is unlikely to explain our findings. The biologically still plausible favorable effects of AET on hippocampal volume in cognitively unimpaired older individuals might be masked by methodological weaknesses and the inclusion of only nine studies. Future studies need to address: the lack of harmonization of hippocampus quantification methods and insufficient power to detect meaningful changes in hippocampal volume across studies.

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