Lower cerebral oxygen utilization is associated with Alzheimer's disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers


Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of oxygen homeostasis that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n=247, 74±7 years, 36% female) and tested whether apolipoprotein E (APOE)-ε4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values>0.05), and OEF interactions with APOE-ε4 status on cognitive and structural imaging outcomes were null (p-values>0.07). However, CMRO2 interacted with APOE-ε4 status on language (p=0.002), executive function (p=0.03), visuospatial (p=0.005), and episodic memory performances (p=0.03), and on hippocampal volume (p=0.006) and inferior lateral ventricle volume (p=0.02). In stratified analyses, lower oxygen metabolism related to worse cognition and smaller grey matter volumes in APOE-ε4 carriers only, with significant effects on the domains of language (p=0.02) and episodic memory performance (p=0.03). Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggests that APOE-ε4 may interact with cerebral oxygen metabolism early in the pathogenesis of Alzheimer’s disease and related neurodegeneration with meaningful clinical consequences.

Submitted to Journal of Cerebral Blood Flow and Metabolism