Cardiorespiratory fitness is associated with cerebral oxygen extraction in Alzheimer’s disease

Cardiorespiratory fitness (CRF) is a modifiable determinant of brain health and has been associated with greater brain volume, improved cognition, and reduced dementia risk. However, whether CRF influences cerebral oxygen extraction fraction (OEF), a marker reflecting the balance between cerebral oxygen delivery and metabolic demand, remains poorly understood in aging and Alzheimer’s disease (AD). We performed a secondary analysis of the Acute Exercise Response on Brain Imaging and Cognition (AEROBIC) study to investigate relationships among CRF, cerebral blood flow (CBF), and OEF in cognitively healthy older adults (CH) and individuals with AD. Multivariable linear regression demonstrated that higher CRF was independently associated with lower OEF. A significant CRF × diagnosis interaction indicated that this relationship was present in AD but not CH. Across the full cohort, higher CBF was strongly associated with lower OEF, and this relationship was preserved across diagnostic groups. Regional analyses demonstrated similar inverse associations between CBF and OEF in multiple cortical regions involved in cognitive and autonomic regulation. These findings suggest that greater CRF may reduce reliance on oxygen extraction by improving the adequacy of cerebral oxygen delivery in AD. Together, CRF, CBF, and OEF provide complementary physiological information regarding cerebral oxygen metabolism and may improve understanding of cerebrovascular physiology in aging and AD.