Insulin and insulin receptors show abundant expression throughout the brain, especially in the hippocampus, which is involved in dementia . Peripheral insulin crosses the blood-brain barrier (BBB) via an active transport mechanism to exert its effects within the CNS . Insulin receptors in the brain are found at synapses on both neurons and astrocytes . Insulin signaling acts as a neuromodulator that regulates the release and reuptake of neurotransmitters, such as acetylcholine and norepinephrine in rat locus coeruleus , and regulates neuronal and glial functions such as synaptogenesis and synaptic plasticity via energy homeostasis, gene expression, and cognition . Interestingly, insulin administered by intranasal improved cognitive dysfunction and insulin signaling, reduced amyloid-β (Aβ) production and amyloid plaque burden, and increased neurogenesis in 4-month-old APP/PS1 mice showing early Alzheimer's disease (AD) pathologies . Furthermore, intranasal insulin application improved cognitive performance in healthy subjects, aged subjects, AD patients, and experimental models of insulin resistance . In the brain, insulin-degrading enzyme (IDE) is synthesized and secreted by neurons, oligodendrocytes, and microglia . IDE degrades extracellular Aβ in microglial and neuronal cultures and insulin can prevent this degradation, thereby impairing the clearance of extracellular Aβ . IDE mutant rats, which show reduced activity of the enzyme, lead to type 2 diabetes, resulting in the enhanced cerebral deposition of Aβ . However, to clarify the precise mechanisms involved in the development of diabetes-induced dementia, further research will be required.