Cardiorespiratory fitness, hippocampal subfield volumes, and mnemonic discrimination task performance in aging

Abstract

Aging and exercise have opposing effects on mnemonic discrimination task performance, which putatively taxes pattern separation mechanisms reliant on the dentate gyrus (DG) subfield of the hippocampus. In young adults, increasing cardiorespiratory fitness (CRF) has been shown to improve mnemonic discrimination task performance and increase left anterior DG/CA3 volume. It is unknown how these variables interact in cognitive aging, yet this knowledge is critical, given the established effects of aging on hippocampal plasticity. To investigate these relationships, 65 older adults (aged 55–85 years) completed a submaximal treadmill test to estimate CRF, a mnemonic discrimination task, and a high‐resolution MRI scan to determine hippocampal subfield volumes. Our older adult sample demonstrated the lowest task accuracy in the condition with the greatest stimuli similarity and left DG/CA3 body volume significantly predicted accuracy in this condition. Our results did not provide support for relationships between CRF and task accuracy or CRF and DG/CA3 volume as evidenced in studies of young adults. Instead, CRF predicted bilateral subiculum volume in older adult women, not men. Altogether, these findings provide further support for a role of the DG in behavioral pattern separation in humans and suggest that CRF may have differential effects on hippocampal subfield integrity in older adult men and women. ClinicalTrials.gov identifiers: (a) Neuroimaging Study of Exercise and Memory Function, NCT02057354; (b) The Entorhinal Cortex and Aerobic Exercise in Aging, NCT02775760; (c) Physical Activity and Cognition Study, NCT02773121.

Daily-life Physical Activity of Young Healthy Adults Associates with Function and Structure of the Hippocampus

“…In addition, Frodl et al (2019) and Nauer et al (2020) found that middle aged and young adults had increased CA4/DG and DG/CA3 volumes to various PA interventions. A common characteristic to these three different results is the use of PA interventions in contrast with the passive measurements of daily PA in Kern et al (2021) and Varma et al (2015). A possible explanation is that PA interventions could have acute effects in some structures, while the daily PA, assessed through VO 2 max, measured daily walking activity and questionnaires, may have another nature of changes that are reflected in the subiculum.…”

“…To sum up, previous research on PA had shown that PA produces changes in the structure and function of the hippocampus (K. Erickson & Kramer, 2009; A. Thomas et al, 2012;Tao et al, 2016;Ikuta et al, 2019;Esteban-Cornejo et al, 2021;Voss, Erickson, et al, 2010;Boraxbekk et al, 2016;Kern et al, 2021) but had barely addressed whether…”

“…Our observation that PA relates to the volume of the CA1 and subicular complex subfields finds resonance in previous studies. For example, Kern et al (2021) studied the relationship between cardiorespiratory fitness, as defined by VO 2 max measures, and hippocampal subfields volumes in elderly participants. They found that VO 2 max measures were associated with increased subicular volume of elderly women.…”

“…However, studies have not found a consistent set of findings that reveal the impact of PA on the hippocampal subfields. For example, some studies have found that PA produced volume increases in the DG/CA3/CA4 (DG: Dentate Gyrus; CA: Cornu Ammonis) subfields (Frodl et al, 2019;Nauer et al, 2020), whereas others have found an impact on other subfields like the Subiculum (SUB) and CA1 (Frodl et al, 2019;Rosano et al, 2017;Nauer et al, 2020;Kern et al, 2021;Varma et al, 2016). In addition, Broadhouse et al (2020) found that 18 months of exercise in patients with mild cognitive impairment halted volume reduction in SUB and reduced loss in CA1 and DG.…”

Strenuous Exercise Habits and Spatial Mnemonic Discrimination Ability in Young Adult Men and Women

“…To our knowledge, our study was the first to directly examine the interaction between gender and exercise on mnemonic discrimination performance, and to report this gender difference (favoring females) in self-reported exercise effects on spatial pattern separation. Prior studies examining mnemonic discrimination and exercise or cardiorespiratory fitness have either controlled for gender as a covariate in the analyses (Bernstein & McNally, 2019; Bullock et al., 2018; Heisz et al., 2017; Kern et al., 2021; Nauer, Schon, et al., 2020; Nauer, Dunne, et al., 2020; Maass et al., 2015; Suwabe, Hyodo, Byun, Ochi, Fukuie, et al., 2017), or did not analyze gender separately (Chaire et al., 2020; Dèry et al., 2013; Kovacevic et al., 2020; Suwabe, Hyodo, Byun, Ochi, Yassa, et al., 2017; Suwabe et al., 2018), perhaps due to limitations in participant sample sizes. In fact, sex differences in exercise effects on cognition have largely been underexplored, especially with regard to memory function (Loprinzi & Frith, 2018).…”