Cerebral oxygen extraction fraction as an emerging imaging biomarker in mild cognitive impairment and dementia

The progressive onset of dementia and mild cognitive impairment (MCI) is a major global health concern due to its profound impact on quality of life. The challenge of identifying MCI and dementia lies partly in the high cost and invasiveness of some biomarkers. In this context, the oxygen extraction fraction (OEF) has emerged as a promising imaging biomarker. This review summarizes current evidence on cerebral OEF as a neuroimaging biomarker in MCI and dementia, focusing on pathophysiology, imaging techniques, comparison with established biomarkers, clinical applications, and future directions. A literature search was conducted from July 1-31, 2025, using the United States National Library of Medicine (PubMed), Scopus, and Web of Science. Search terms included "oxygen extraction fraction" OR "cerebral oxygen metabolism" AND ("mild cognitive impairment" OR "MCI" OR dementia OR "Alzheimer's disease" OR "vascular dementia") AND (qBOLD OR TRUST MRI OR mcQQ MRI OR 15O PET). English-language studies from the past ten years reporting OEF in cognitive impairment were included; case reports and non-human studies were excluded. OEF demonstrates distinct alterations across the spectrum of cognitive impairment. In MCI, reduced OEF has been linked to impaired neurovascular coupling and mitochondrial dysfunction. In dementia, patterns diverge - typically reduced in Alzheimer's disease but heterogeneous in vascular conditions, often elevated under chronic hypoperfusion yet reduced when vascular pathology coexists with Alzheimer's disease. Non-invasive techniques such as mcQQ magnetic resonance imaging (MRI) and TRUST MRI estimate OEF, while ¹⁵O PET remains the gold standard. OEF shows promise as a neuroimaging biomarker for early detection, differential classification, and monitoring disease progression in cognitive impairment.