Metabolic rates of glucose in the brain networks of healthy adults vary as a function of age and levels of peripheral insulin resistance, and predict cognition

Research suggests that cerebral metabolic rates of glucose (CMRGLC) decline with age. However, only a small body of research has taken into account partial volume effects in PET imaging and age-related reductions in cortical thickness. Separate research suggests that levels of peripheral insulin resistance may be a biomarker for functional brain changes. Thirty-six younger (mean 27.8 years) and 43 older (mean 75.5) participants completed a blood and cognitive tests battery and a simultaneous 90-minute MR/PET scan. Cortical thickness and CMRGLC were derived using the Schaefer 100 atlas, and major subcortical structures. Insulin resistance was measured with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Older adults had lower CMRGLC than younger adults across most regions, an effect that was mediated in part but not in full by age-related lower cortical thickness. Age x HOMA-IR interaction analysis showed that a 10% increase in insulin resistance was associated with 2% to 8% lower CMRGLC in younger adults across regions, with smaller reductions in older adults. Higher CMRGLC in the ventral attention, control and default networks was associated with better executive function, attention and processing seed. These results suggest that the age-related cerebral metabolism reductions are partly mediated by cortical atrophy, whereas insulin resistance associations with CMRGLC are moderated by age. ### Competing Interest Statement The authors have declared no competing interest.