Regional oxygen extraction fraction is higher in older adults with type 2 diabetes and obesity: associations with cognition and metabolic markers

Type 2 diabetes (T2D) and obesity are highly prevalent among older adults and associated with increased Alzheimer's disease and related dementia (ADRD) risk, but underlying mechanisms linking T2D and obesity to cognitive impairment remain partially understood. Quantitative susceptibility mapping (QSM)-derived oxygen extraction fraction (OEF) provides a noninvasive MRI-based marker of cerebral metabolism and may capture early alterations in brain physiology. In this single-center, cross-sectional pilot study, we examined QSM-derived OEF in older adults with T2D + obesity (N = 14) and age- and sex-matched controls (N = 18) and evaluated associations with blood markers and cognitive performance. Whole-brain OEF was higher in participants with T2D + obesity (29.5% vs 27.3%; p = 0.019), with higher OEF observed across all examined lobar regions (p < 0.05). The T2D + obesity group demonstrated lower Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention (p = 0.035) and Global Cognition (p = 0.022) indices and lower Delis-Kaplan Executive Function System (D-KEFS) Color-Word Switching (p = 0.001) scores. Whole-brain OEF was positively associated with leptin (p = 0.018) and negatively associated with HDL (p = 0.030). Higher regional OEF significantly correlated with lower cognitive performance, particularly D-KEFS (r = -0.40 to -0.62) and RBANS Attention (r = -0.36 to -0.41). This is the first study to support a potential link between altered cerebral oxygen extraction, metabolic dysfunction, and cognitive performance in older adults with T2D and obesity. Larger, longitudinal studies are needed to confirm these associations and determine their relevance to cognitive decline and ADRD risk.