Intranasal Insulin Reaches Brain Regions Tied to Memory

A new imaging study from Wake Forest University School of Medicine has shown that insulin administered intranasally can reach specific brain regions associated with memory and cognition in older adults. The study, published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, also indicates that insulin uptake differs between individuals with mild cognitive impairment and those without.

Using positron emission tomography (PET) and a radiolabeled insulin tracer, researchers tracked the distribution of intranasal insulin in the brains of 16 participants aged around 72 years. Seven participants were cognitively healthy, and nine had been diagnosed with mild cognitive impairment. All received insulin labeled with a gallium-based radiotracer, [68Ga]Ga-NOTA-insulin, administered using a six-spray nasal device.

Brain scans taken during the 40-minute protocol revealed that the insulin reached 11 regions critical for memory processing and cognitive function, including the hippocampus, amygdala and temporal cortex. This direct evidence addresses a long-standing challenge in earlier studies that lacked confirmation of whether the intranasal treatment had successfully reached its intended neural targets.

“This study fills a critical gap in our understanding of how intranasal insulin reaches the brain.”

Dr. Suzanne Craft.

Differences in uptake patterns seen in mild cognitive impairment

Researchers observed distinct uptake and clearance patterns based on cognitive status. In cognitively normal individuals, insulin delivery was more sustained, while those with mild cognitive impairment showed a rapid initial uptake followed by faster clearance from the brain. These differences suggest that disease progression may alter how insulin is transported or retained in neural tissues.

“We needed direct evidence that the drug is able to reach key brain targets. An unexpected finding was the observation that uptake may differ in people with early cognitive decline.”

Dr. Suzanne Craft.

Additional exploratory findings indicated that cardiovascular health markers in women were positively associated with insulin uptake in the brain. Conversely, higher levels of plasma ptau217, a biomarker linked to amyloid accumulation in Alzheimer’s disease, correlated with reduced insulin absorption in multiple brain regions.

Delivery method is well-tolerated and may support future clinical trials

The nasal delivery system used in the study was rated as easy to use by participants, and only two individuals reported mild headaches that resolved within a day. The overall safety profile supports further exploration of intranasal insulin in clinical trials.

Validating the ability of a delivery system to target specific brain regions is a critical step before launching therapeutic trials. These findings also offer potential insight into why intranasal insulin has shown varying effects across individuals in previous studies. Researchers are planning larger studies to investigate how factors such as vascular health, amyloid load and biological sex may affect insulin uptake.

“While there’s still a lot to learn, these findings show that we now have the tools to validate intranasal drug delivery to the brain.”

Dr. Suzanne Craft.

The imaging protocol could be adapted to evaluate other intranasally delivered agents intended for neurological disorders, offering a framework to confirm drug targeting and retention in the central nervous system.

Reference: Sai KKS, Erichsen JM, Gollapelli KK, et al. First‐in‐human positron emission tomography study of intranasal insulin in aging and MCI. A&D Transl Res & Clin Interv. 2025;11(3). doi: 10.1002/trc2.70123

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