Cardiorespiratory fitness and mnemonic discrimination across the adult lifespan

Abstract

With a rising aging population, it is important to develop behavioral tasks that assess and track cognitive decline, and to identify protective factors that promote healthy brain aging. Mnemonic discrimination tasks that rely on pattern separation mechanisms are a promising metric to detect subtle age-related memory impairments. Behavioral performance on these tasks rely on the integrity of the hippocampus and surrounding circuitry, which are brain regions known to be adversely affected in aging and neurodegenerative disorders. Aerobic exercise, which improves cardiorespiratory fitness (CRF), has been shown to counteract aging-related decreases in structural and functional brain integrity and attenuate decline of cognitive performance. Here, we tested the hypothesis that higher CRF attenuates age-related deficits in mnemonic discrimination in both a nonspatial mnemonic discrimination (Mnemonic Similarity Task) and a virtual navigation task (Route Disambiguation Task). Importantly, we included individuals across the lifespan (aged 18-83 yr), including the middle-age range, to determine mnemonic discrimination performance across adulthood. Participants completed two mnemonic discrimination tasks and a treadmill test to assess CRF. Our results demonstrate robust negative age-related effects on mnemonic discrimination performance across both the nonspatial and spatial domains. Critically, higher CRF mitigated age-related attenuation in spatial contextual discrimination task performance, but did not show an attenuation effect on performance for object-based mnemonic discrimination. These results suggest that performance on spatial mnemonic discrimination may be a useful tool to track vulnerability in older individuals at risk for cognitive decline, and that higher CRF may lead to cognitive preservation across the adult lifespan, particularly for spatial disambiguation of similar contexts.

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

“…Given this proposed role of the subiculum in spatial navigation, it stands to reason that if cardiorespiratory fitness modulates subicular integrity, cardiorespiratory fitness may also modulate performance on spatial navigation tasks. Importantly, such a relationship has been demonstrated, as a recent behavioral study indicated that greater cardiorespiratory fitness was associated with better performance on a spatial route disambiguation task in older adults (Nauer, Schon, & Stern, 2020). Thus, future studies should examine the relationships between cardiorespiratory fitness, subiculum volume, and spatial navigation to determine if subicular integrity may modulate observed relationships between cardiorespiratory fitness and spatial navigation task performance.…”

“…A consistently growing body of literature indicates that aging is associated with significant impairments on tasks designed to putatively measure behavioral pattern separation (Holden, Toner, Pirogovsky, Kirwan, & Gilbert, 2013; Nauer, Schon, & Stern, 2020; Stark et al, 2013; Stark & Stark, 2017; Toner, Pirogovsky, Kirwan, & Gilbert, 2009; Yassa et al, 2011; Yassa & Stark, 2011). To build upon these studies, our older adult participants completed an MDT designed to behaviorally tax pattern separation at parametrically varying levels of stimuli similarity.…”

“…Second, it is possible that the link between cardiorespiratory fitness and mnemonic discrimination is domain‐specific. A study from our laboratory recently demonstrated that although aging is associated with impaired mnemonic discrimination in both spatial and nonspatial domains, greater cardiorespiratory fitness was associated with an attenuated age‐related decline in spatial contextual discrimination only (Nauer, Schon, & Stern, 2020). It has been established that the hippocampus is involved in two neocortical systems for memory: the posterior medial system, in which contextual information is processed through the parahippocampal cortex and medial entorhinal cortex, then converges upon the hippocampus, and the anterior temporal system, in which item information is processed through the perirhinal cortex and lateral entorhinal cortex, then converges upon the hippocampus (Hunsaker, Chen, Tran, & Kesner, 2013; for reviews see Ranganath & Ritchey, 2012; Ritchey, Libby, & Ranganath, 2015).…”

“…Before testing at the Boston University Fitness and Recreation Center, study staff instructed participants to refrain from aerobic exercise and/or resistance training for 24 hr prior to testing and refrain from any caffeine consumption for 3 hr prior to testing. The incremental treadmill test protocol implemented by our laboratory (Kronman et al, 2020; Nauer, Dunne, et al, 2020; Nauer, Schon, & Stern, 2020) includes three phases: 3 min of warm‐up, approximately 8–12 min of incremental exercise, and 3 min of cool‐down. Throughout the duration of the test, a study staff member monitored the participant's heart rate.…”

“…This process is thought to rely on the dentate gyrus (DG), the hippocampal subfield that demonstrates neurogenesis throughout the adult lifespan (Boldrini et al, 2018; Eriksson et al, 1998; Spalding et al, 2013; for opposing perspective, see Sorrells et al, 2018). Cognitive aging is also associated with decreased accuracy on mnemonic discrimination tasks (Nauer, Schon, & Stern, 2020; Stark & Stark, 2017; Stark, Yassa, Lacy, & Stark, 2013; Yassa et al, 2011; Yassa & Stark, 2011), which are behavioral paradigms designed to tax pattern separation. Mechanistically, it is likely that this behavioral impairment is related to the vulnerability of the DG subfield in aging.…”