Investigators will test the effects of insulin administered through a nasal spray to enhance memory function in patients with early stage Alzheimer’s disease (AD), and they will use conventional brain functional MRI (fMRI) and Arterial Spin Labeling (ASL) imaging techniques to assess underlying responses in the brain’s hippocampus that are associated with the treatment’s effects.
While insulin immediately brings to mind diabetes, insulin also has a major role in the brain. The brain’s hippocampus, where memory and learning functions occur, has many insulin receptors. Prior research has established that insulin signaling is involved in synaptic plasticity and strength. It influences receptors for several neurotransmitters, and insulin receptors are activated during short-term memory. Based on these observations, the investigators hypothesize that memory loss in AD patients may be associated with low brain insulin levels and that intranasal insulin administration (which goes directly into the brain but not the rest of the body) will enhance memory performance through increased functional activation in the medial temporal lobe of the hippocampus. They also hypothesize that the treatment will be effective in AD patients who do not have the apoE4 gene, which genetically predisposes people to AD, but will not be effective in patients who have this gene.
They will enroll 36 patients, 24 with early stage AD (50 percent with the apoE4 gene and 50 percent without it) and 12 healthy adult participants. No participants will have diabetes, since diabetes alters insulin signaling. After memory testing, participants will undergo fMRI scans and cognitive testing on two occasions, after receiving intranasal insulin on one occasion and intranasal placebo on the other. The investigators will compare performance on cognitive tests and fMRI hippocampal activation when participants receive insulin vs. placebo. ASL imaging will be used to assess the role of altered cerebral blood flow to account for global changes in cortical activity related to insulin administration. These tests will provide a preliminary indication about insulin’s role in memory functions, how the brain responds to intranasal insulin therapy in early AD, and whether the therapy should be pursued in AD patients who do not have the apoE4 gene, but not in those with the gene.
Significance: If preliminary results indicate that intranasal insulin administration enhances memory function in patients with early AD who do not have the apoE4 gene, the study could lead to large-scale tests of this potential new therapy in that population.