Cardiorespiratory Fitness, Hippocampal Subfield Volumes, and Pattern Separation Task Performance in Older Adults

Abstract

Cognitive aging is associated with reduced integrity of the medial temporal lobe memory system. A key facet of episodic memory that demonstrates behavioral impairment with aging is pattern separation (PS), or the disambiguation of similar stimuli during neural encoding. PS is supported by the dentate gyrus (DG), a subfield of the hippocampus that demonstrates striking plasticity in response to exercise. Recent work from our laboratory has demonstrated that increasing cardiorespiratory fitness (CRF) through exercise training is associated with increased left anterior DG/CA3 volume and improved PS task performance in young adults. However, how these variables interact in cognitive aging is unknown, yet critical, given that aging is associated with impairments in hippocampal plasticity and PS task performance. Based on our findings in young adults, we predicted that CRF would positively correlate with DG/CA3 volume and PS task performance in older adults. Secondly, given the suggested role of the DG in PS task performance in humans, we predicted that DG/CA3 volume would significantly correlate with PS task performance. Sixty‐four participants aged 55–85 years underwent a submaximal treadmill test to estimate maximal oxygen uptake (VO2MAX), which operationally defined CRF, an MRI scan to examine volume of the hippocampal subfields, and a behavioral task designed to tax PS at parametrically varying levels of stimulus similarity (10, 30, 50%). There was a significant effect of similarity on PS task performance, with participants demonstrating lowest task accuracy in the condition theoretically placing the highest taxation on PS (50%). Left DG/CA3 body volume significantly predicted performance in the 50% condition. However, there was no relationship between CRF and PS task performance. Furthermore, while CRF did not predict DG/CA3 volume, it did significantly predict right and left subiculum volume, which may be unique to female participants between the ages of 60–80 years. Altogether, these findings provide support for a role of the DG in PS in older adults and suggest a relationship between CRF and hippocampal subfield volume that may be unique to the bilateral subiculum in female older adults. Support or Funding Information This work was supported by NIH grant R00 AG036845 (Schon), R21 AG049968 (Schon), and the BU Clinical and Translational Science Institute (1UL1TR001430).