Peripheral insulin resistance attenuates cerebral glucose metabolism and impairs working memory in healthy adults

People with insulin resistance are at increased risk for cognitive decline. Insulin resistance has previously been considered primarily a condition of ageing but it is increasingly seen in younger adults. It is possible that impaired insulin function in early adulthood has both proximal effects and moderates or even accelerates changes in cerebral metabolism in ageing. Thirty-six younger (mean 27.8 years) and 43 older (mean 75.5) participants completed a battery of tests, including blood sampling, cognitive assessment and a simultaneous PET/MR scan. Cortical thickness and cerebral metabolic rates of glucose were derived for 100 regions and 17 functional networks. Older adults had lower rates of regional cerebral glucose metabolism than younger adults across the brain even after adjusting for lower cortical thickness in older adults. Higher fasting blood glucose was also associated with lower regional cerebral glucose metabolism in older adults. In younger adults, higher insulin resistance was associated with lower rates of regional cerebral glucose metabolism but this was not seen in older adults. The largest effects of insulin resistance in younger adults were in prefrontal, parietal and temporal regions; and in the control, salience ventral attention, default and somatomotor networks. Higher rates of network glucose metabolism were associated with lower reaction time and psychomotor speed. Higher levels of insulin resistance were associated with lower working memory. Our results underscore the importance of insulin sensitivity and glycaemic control to brain health and cognitive function across the adult lifespan, even in early adulthood.