The brain is an insulin-sensitive organ and brain insulin-resistance is associated with cognitive decline, while impaired cerebrovascular function is an important event preceding the development of impaired cognitive performance. Brain insulin-sensitivity can be assessed by quantifying acute effects of insulin as nasal spray on (regional) cerebral blood flow (CBF), which is a well-validated marker for cerebrovascular function. However, the specific brain regions that respond to nasal insulin are largely unknown, while it is also relevant to investigate the relationship between (regional) brain insulin-sensitivity and cognitive performance.

Therefore, we systematically reviewed randomized, placebo-controlled intervention trials (RCTs) involving adults that assessed potential insulin-induced changes in CBF and cognitive performance. Three studies reported acute effects of intranasal insulin on whole-brain CBF, but no effects were observed. Seven studies reported the acute impact of nasal insulin administration on regional CBF. These studies found pronounced increases in CBF in the inferior frontal gyrus, dorsal striatum and insular cortex, while a decreased CBF was found around the middle frontal gyrus and hypothalamus. These responses were dependent on the presence of risk factors for the development of peripheral insulin-resistance, which may indicate a close relation between peripheral and brain insulin-sensitivity.

Furthermore, RCTs reported insulin-induced acute and longer-term benefits for executive function and memory, but it is too preliminary to draw any conclusions for a relationship between regional brain-insulin sensitivity and cognitive performance. In summary, we identified insulin-induced changes in CBF in specific brain regions that indicates regional brain insulin-sensitivity, which may imply that these brain regions are sensitive targets for interventions aimed to prevent cognitive decline. Future research should now focus on the longer-term application of nasal insulin on regional changes in CBF and establish a potential relationship with cognitive performance.