Cardiorespiratory fitness and hippocampal volume predict faster episodic associative learning in older adults.

Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate on the episodic associative learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show higher CRF was associated with faster learning rate. Larger hippocampal volume was also associated with faster learning rate, though hippocampal volume did not mediate the relationship between CRF and learning rate. Furthermore, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found learning rate on the EAL task was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time, we show that both higher CRF and larger hippocampal volume in healthy older adults are related to enhanced rate of relational memory acquisition.

Association between cardiorespiratory fitness and cerebrovascular reactivity to a breath-hold stimulus in older adults: influence of aerobic exercise training.

Cerebrovascular reactivity (CVR) to a physiological stimulus is a commonly used surrogate of cerebrovascular health. Cross-sectional studies using blood oxygen level dependent (BOLD) neuroimaging demonstrated lower BOLD-CVR to hypercapnia among adults with high compared with lower cardiorespiratory fitness (CRF) in contrast to transcranial Doppler studies. However, whether BOLD-CVR changes following chronic aerobic exercise in older, cognitively intact adults is unclear. This study evaluated relations between BOLD-CVR with CRF (V̇o2peak) using a cross-sectional and interventional study design. We hypothesized that 1) greater CRF would be associated with lower BOLD-CVR in older adults (n = 114; 65 ± 6.5 yr) with a wide range of CRF and 2) BOLD-CVR would be attenuated after exercise training in a subset (n = 33) randomized to 3-mo of moderate- or light-intensity cycling. CVR was quantified as the change in the BOLD signal in response to acute hypercapnia using a blocked breath-hold design from a region-of-interest analysis for cortical networks. In the cross-sectional analysis, there was a quadratic relation between V̇o2peak (P = 0.03), but not linear (P = 0.87) and cortical BOLD-CVR. BOLD-CVR increased until a V̇o2peak ∼28 mL/kg/min after which BOLD-CVR declined. The nonlinear trend was consistent across all networks (P = 0.04-0.07). In the intervention, both the active and light-intensity exercise groups improved CRF similarly (6% vs. 10.8%, P = 0.28). The percent change in CRF was positively associated with change in BOLD-CVR in the default mode network only. These data suggest that BOLD-CVR is nonlinearly associated with CRF and that in lower-fit adults default mode network may be most sensitive to CRF-related increases in BOLD-CVR.NEW & NOTEWORTHY Earlier studies evaluating associations between cardiorespiratory fitness (CRF) and cerebrovascular reactivity (CVR) have demonstrated conflicting findings dependent on imaging modality or subject characteristics in individuals across a narrow range of CRF. This study demonstrates that CRF is nonlinearly associated with CVR measured by blood oxygen level dependent (BOLD) fMRI in a large sample of middle-aged and older adults across a wide range of CRF, suggesting that conflicting prior findings are related to the range of CRFs studied.

Acute Exercise Effects Predict Training Change in Cognition and Connectivity.

PURPOSE: Previous studies report memory and functional connectivity of memory systems improve acutely after a single aerobic exercise session or with training, suggesting that the acute effects of aerobic exercise may reflect initial changes that adapt over time. In this trial, for the first time, we test the proof-of-concept of whether the acute and training effects of aerobic exercise on working memory and brain network connectivity are related in the same participants. METHODS: Cognitively normal older participants (N = 34) were enrolled in a randomized clinical trial (NCT02453178). Participants completed fMRI resting state and a face working memory N-back task acutely after light- and moderate-intensity exercises and after a 12-wk aerobic training intervention. RESULTS: Functional connectivity did not change more after moderate-intensity training compared with light-intensity training. However, both training groups showed similar changes in cardiorespiratory fitness (CRF) (maximal exercise oxygen uptake, V˙O2peak), limiting group-level comparisons. Acute effects of moderate-intensity aerobic exercise on connections primarily in the default network predicted training enhancements in the same connections. Working memory also improved acutely, especially after moderate-intensity, and greater acute improvements predicted greater working memory improvement with training. Exercise effects on functional connectivity of right lateralized frontoparietal connections were related to both acute and training gains in working memory. CONCLUSIONS: Our data support the concept of acute aerobic exercise effects on functional brain systems and performance as an activity-evoked biomarker for exercise training benefits in the same outcomes. These findings may lead to new insights and methods for improving memory outcomes with aerobic exercise training.