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.

Keywords: MRI; aging; cardiorespiratory fitness; hippocampus; mnemonic discrimination; pattern separation.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any interest or relationship, financial or otherwise, that may be perceived as influencing an author's objectivity.

© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Figures

FIGURE 1

Example of hippocampal head and body subfield segmentations. The hippocampus was automatically segmented into the following subfields: Cornu Ammonis (CA) 1–3 (CA1, CA2, CA3), dentate gyrus (DG), and subiculum (SUB). ROIs for analyses included CA1, DG/CA3, and SUB. Next, the hippocampal subfields were manually segmented into the head, body, and tail using established anatomic guidelines. Subfield delineations in the tail were not used for analyses due to low reliability within and between participants

FIGURE 2

Distribution of cardiorespiratory fitness, as measured by estimated maximal oxygen uptake (V˙O2max), for a sample of 53 older adults separated by sex. Fifty‐three participants successfully completed the submaximal treadmill test to estimate V˙O2max, which operationally defined cardiorespiratory fitness. Mean estimated V˙O2max over all participants was 29.31 ± 6.08 ml kg−1 min−1 (mean ± SD). Estimated V˙O2max varied significantly by sex, such that men demonstrated significantly higher estimated V˙O2max with a mean of 31.84 ± 6.08 ml kg−1 min−1 compared to women with a mean of 27.89 ± 5.69 ml kg−1 min−1 (t[35.276] = 2.322, p = .026*). This figure demonstrates the variability within estimated V˙O2max values of participants

FIGURE 3

Mnemonic discrimination task, behavioral results, and the relationship between behavior and DG/CA3 body volume. (a) Stimuli similarity was parametrically manipulated by morphing each face to a trial unique template at low (10%), moderate (30%), or high (50%) similarity. (b) An example trial of the mnemonic discrimination task. Half of the trials were nonmatch trials, in which the Test face was not the same as Sample 1 or Sample 2 (as demonstrated above), and half of the trials were match trials, in which the Test face was the same as either Sample 1 or Sample 2 (ITI, inter‐trial interval) (c) Older adults demonstrated significantly decreased accuracy in the 50% MDT condition, the condition with the greatest mnemonic discrimination requirement. (Analysis of variance demonstrated a significant effect of similarity on task performance (F = 39.75, p < .001***); post hoc testing using a Tukey multiple comparisons of means indicated that average corrected accuracy in the 50% MDT condition was significantly lower than in the 30% MDT condition (p < .01**) and the 10% MDT condition (p < .001***).) (d) Left DG/CA3 body volume significantly predicted corrected accuracy in the 50% MDT condition (N = 19, L DG/CA3 body vol t[14] = 3.051, p = .009**, delta‐R2 = 0.303; model F4,14 = 4.167, adjusted R2 = 0.413)

FIGURE 4

Cardiorespiratory fitness, as measured by V˙O2max, significantly predicted bilateral ICV‐corrected subiculum volume in women. (a) V˙O2max significantly predicted bilateral subiculum volume in women (N = 21, estimated V˙O2maxt[16] = 2.645, p = .018*, delta‐R2 = 0.232; model F4,16 = 3.548, adjusted R2 = 0.338). (b) The association between subiculum volume and the interaction between estimated V˙O2max and sex was trending toward significance (N = 34, V˙O2max: Sex t[27] = 1.910, p = .067†, delta‐R2 = 0.089; model F6,27 = 2.367, adjusted R2 = 0.199). Estimated V˙O2max did not significantly predict subiculum volume in this model (estimated V˙O2maxt[27] = −0.604, p = .551)