Change in cardiorespiratory fitness, hippocampal subfields and virtual navigation in older adults: a randomized controlled trial

Abstract

AbstractBackgroundHippocampal neuroplasticity is oppositely affected by aging and exercise. Rodent models have demonstrated a specific exercise‐induced neuroplasticity enhancement in the dentate gyrus (DG) subfield of the hippocampus associated with improved spatial memory. In humans, exercise‐induced enhancement in cardiorespiratory fitness (CRF) has been shown to increase the left anterior DG volume among young adults. Cross‐sectional studies in older adults showed that higher CRF is associated with greater subiculum volume in women and attenuated age‐related decline in performance of hippocampus‐dependent spatial navigation tasks. However, it is unknown whether these relationships hold for exercise‐induced enhancement in CRF among older adults.MethodIn this study, 32 older adults who completed one of two randomized controlled trials (RCT; ClinicalTrials.gov; NCT02057354; NCT02775760) participated in a 12‐week moderate‐intensity, trainer‐supervised exercise training program. Participants were randomized into two groups, active control (resistance training; RT) and endurance training (ET). The aim of this RCT was to examine the effects of exercise training and training‐induced increases in CRF on hippocampal subfield volumes and activation during virtual navigation in cognitively‐healthy sedentary older adults (55‐85 years old) using structural MRI and fMRI. FreeSurfer 7.1 was used to automatically segment hippocampal subfields using T1 and high‐resolution T2‐weighted images. AFNI 19.0 was used for fMRI preprocessing and analyses.ResultOur structural MRI results demonstrated that after the 12‐week period, the RT but not the ET group showed a marginally significant volume decrease in the right anterior DG. Additionally, CRF increase was significantly associated with volume increase in the left anterior subiculum among women. Our fMRI results showed that CRF increase predicted a marginally significant lower fMRI activation in the left subiculum. Finally, an exploratory whole‐brain fMRI analysis showed that CRF increase significantly predicted lower activation in the cuneus and right inferior frontal gyrusConclusionOur results extend findings from animal models on DG neuroplasticity to older adult humans and to brain areas associated with spatial navigation. Furthermore, our results suggest that exercise and CRF may attenuate aging‐related decline in the structural and functional integrity of hippocampal subfields among older adults, especially among women, and possibly by targeting the subiculum.