Estimated glucose disposal rate is associated with brain aging and dementia among diabetes-free older adults.

BACKGROUND: To investigate the association of estimated glucose disposal rate (eGDR), a validated measure of insulin resistance (IR), with brain aging and dementia among diabetes-free people. METHODS: This study included 258 732 diabetes- and dementia-free adults aged ≥55 from UK Biobank, including 15 389 participants who underwent brain MRI scans. eGDR was assessed by a well-established formula. Brain age gap (BAG) was calculated as difference between machine learning-predicted brain age and chronological age. Dementia was ascertained based on medical records. Data were analyzed using Cox, Laplace, and linear regression. RESULTS: Over the follow-up, 7063 participants developed dementia. The hazard ratios of dementia for eGDR quartiles 2-4 compared to eGDR quartile 1 were 0.88 (0.81, 0.96), 0.83 (0.76, 0.92), and 0.73 (0.66, 0.82), respectively. High eGDR was further associated with 1.31 (0.81, 1.80) years later onset of dementia. Those with high eGDR had 2.09 (1.74, 2.45) years younger brain age than chronological age. Among APOE ɛ4 carriers, those with high eGDR had 14% lower incidence of dementia and a 1.77-year gap between brain age and chronological age (p-for-interaction < .001). CONCLUSION: Higher eGDR is associated with prolonged onset of dementia and delayed brain aging among diabetes-free individuals, and could buffer genetic risk of APOE ɛ4.