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However, less is known about the impact of cardiorespiratory fitness on medial temporal lobe extrahippocampal neocortical regions. Specifically, it is unclear how cardiorespiratory fitness modulates these brain regions in young adulthood and if these regions are differentially related to cardiorespiratory fitness in young versus older adults. The primary goal of this study was to investigate if cardiorespiratory fitness predicted medial temporal lobe cortical thickness which, with the hippocampus, are critical for spatial learning and memory. Additionally, given the established role of these cortices in spatial navigation, we sought to determine if cardiorespiratory fitness and medial temporal lobe cortical thickness would predict greater subjective sense of direction in both young and older adults. Cross\u2010sectional data from 56 young adults (20\u201335\u2009years) and 44 older adults (55\u201385\u2009years) were included. FreeSurfer 6.0 was used to automatically segment participants' 3T T1\u2010weighted images. Using hierarchical multiple regression analyses, we confirmed significant associations between greater cardiorespiratory fitness and greater left entorhinal, left parahippocampal, and left perirhinal cortical thickness in young, but not older, adults. Left parahippocampal cortical thickness interacted with age group to differentially predict subjective sense of direction in young and older adults. Young adults displayed a positive, and older adults a negative, correlation between left parahippocampal cortical thickness and sense of direction. Our findings extend previous work on the association between cardiorespiratory fitness and hippocampal subfield structure in young adults to left medial temporal lobe neocortical regions.<\/jats:p>","DOI":"10.1111\/ejn.16200","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T08:39:21Z","timestamp":1701938361000},"page":"82-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiorespiratory fitness is associated with cortical thickness of medial temporal brain areas associated with spatial cognition in young but not older adults"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-1694","authenticated-orcid":false,"given":"Michael A.","family":"Rosario","sequence":"first","affiliation":[{"name":"Graduate Program for Neuroscience Boston University Aram V. 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