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 in 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 that higher CRF was associated with larger hippocampal volume and faster learning rate. Larger hippocampal volume was also associated with faster learning rate, and hippocampal volume partially mediated the relationship between CRF and learning rate. Further, 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 that EAL learning rate 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 higher CRF in healthy older adults is related to enhanced rate of relational memory acquisition, in part mediated by benefits on the hippocampus.

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