New study validates insulin nasal spray to deliver Alzheimer’s drug directly to the brain

A groundbreaking brain imaging study from Wake Forest University School of Medicine confirms a vital step toward new Alzheimer’s disease treatments: Intranasal insulin, delivered via a simple nasal spray, safely and effectively reaches key memory regions of the brain in older adults. The study also revealed that people with early cognitive decline absorb it differently.

This research, published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, describes the results of a milestone positron emission tomography (PET) imaging study.

It directly shows that intranasal insulin travels to 11 key brain regions associated with memory and cognition. Previously, researchers faced challenges in earlier intranasal insulin trials because they couldn’t confirm if the treatment was reaching its brain targets.

“This study fills a critical gap in our understanding of how intranasal insulin reaches the brain,” said Suzanne Craft, Ph.D., professor of gerontology and geriatric medicine at Wake Forest University School of Medicine and director of the Wake Forest Alzheimer’s Disease Research Center. According to Craft, insulin resistance is a known risk factor for Alzheimer’s disease.

“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,” Craft said. “This means we’re no longer flying blind; we now have a roadmap directly to the brain.”

The study involved 16 older adults (average age 72), including seven who were cognitively normal and nine with mild cognitive impairment (MCI). Using a novel radiotracer, [68Ga]Ga-NOTA-insulin, delivered with a specialized six-spray nasal system, participants underwent a 40-minute brain PET scan followed by whole-body imaging. Participants described the nasal spray as “surprisingly easy.”

The researchers found:

• Elevated insulin uptake in critical memory and cognition areas, including the hippocampus, olfactory cortex, amygdala and temporal lobe.
• Cognitively normal individuals showed higher uptake and distinct timing patterns of insulin delivery compared to those with MCI, who exhibited rapid initial uptake followed by quicker clearance.
• In women, insulin uptake correlated strongly with factors linked to healthy cardiovascular function and elevated ptau217 levels (a marker of brain amyloid, the sticky protein that accumulates in the brain in Alzheimer’s disease) were associated with decreased brain absorption across multiple regions.
• Only two participants reported mild headaches post-scan, which resolved within 24 hours, indicating the procedure was well-tolerated.

“One of the biggest challenges in developing treatments for brain diseases is getting agents into the brain,” Craft said. “This study shows we can validate intranasal delivery systems effectively, an essential step before launching therapeutic trials.”

Given recent concerns around the limited efficacy and side-effect profiles of some anti-amyloid drugs, this validation strategy supports a broader approach to Alzheimer’s treatment, including metabolic and delivery-focused interventions. The findings could help explain why some patients respond better to intranasal insulin therapy than others, potentially leading to personalized treatment approaches.

“There’s an urgent need to identify effective and feasible ways to prevent and treat Alzheimer’s dementia,” said Craft. “These findings show that we can now validate whether treatments are actually reaching their intended brain targets, which is critical information for designing successful trials.”

The imaging protocol used a precision nasal delivery system supplied by Aptar Pharma and could be adapted for other intranasal therapies targeting neurological disorders.

“The results of the study represent a significant step forward in medicine as they validate that our nasal delivery system was effective in delivering intranasal insulin safely and effectively to specific regions of the brain,” said Reenal Gandhi, director of business development for Aptar Pharma.

“As scientific understanding and development advance, we see continued opportunities for intranasal delivery to improve how therapeutics are delivered to the central nervous system.”

The Wake Forest University School of Medicine team is now planning larger validation studies within the next 12–18 months to explore how vascular health, amyloid accumulation and sex differences influence brain insulin delivery.

“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,” Craft said. “This is promising news for developing more effective and accessible treatments for Alzheimer’s disease.”

A groundbreaking brain imaging study from Wake Forest University School of Medicine confirms a vital step toward new Alzheimer’s disease treatments: Intranasal insulin, delivered via a simple nasal spray, safely and effectively reaches key memory regions of the brain in older adults. The study also revealed that people with early cognitive decline absorb it differently.

This research, published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, describes the results of a milestone positron emission tomography (PET) imaging study.

It directly shows that intranasal insulin travels to 11 key brain regions associated with memory and cognition. Previously, researchers faced challenges in earlier intranasal insulin trials because they couldn’t confirm if the treatment was reaching its brain targets.

“This study fills a critical gap in our understanding of how intranasal insulin reaches the brain,” said Suzanne Craft, Ph.D., professor of gerontology and geriatric medicine at Wake Forest University School of Medicine and director of the Wake Forest Alzheimer’s Disease Research Center. According to Craft, insulin resistance is a known risk factor for Alzheimer’s disease.

“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,” Craft said. “This means we’re no longer flying blind; we now have a roadmap directly to the brain.”

The study involved 16 older adults (average age 72), including seven who were cognitively normal and nine with mild cognitive impairment (MCI). Using a novel radiotracer, [68Ga]Ga-NOTA-insulin, delivered with a specialized six-spray nasal system, participants underwent a 40-minute brain PET scan followed by whole-body imaging. Participants described the nasal spray as “surprisingly easy.”

The researchers found:

• Elevated insulin uptake in critical memory and cognition areas, including the hippocampus, olfactory cortex, amygdala and temporal lobe.
• Cognitively normal individuals showed higher uptake and distinct timing patterns of insulin delivery compared to those with MCI, who exhibited rapid initial uptake followed by quicker clearance.
• In women, insulin uptake correlated strongly with factors linked to healthy cardiovascular function and elevated ptau217 levels (a marker of brain amyloid, the sticky protein that accumulates in the brain in Alzheimer’s disease) were associated with decreased brain absorption across multiple regions.
• Only two participants reported mild headaches post-scan, which resolved within 24 hours, indicating the procedure was well-tolerated.

“One of the biggest challenges in developing treatments for brain diseases is getting agents into the brain,” Craft said. “This study shows we can validate intranasal delivery systems effectively, an essential step before launching therapeutic trials.”

Given recent concerns around the limited efficacy and side-effect profiles of some anti-amyloid drugs, this validation strategy supports a broader approach to Alzheimer’s treatment, including metabolic and delivery-focused interventions. The findings could help explain why some patients respond better to intranasal insulin therapy than others, potentially leading to personalized treatment approaches.

“There’s an urgent need to identify effective and feasible ways to prevent and treat Alzheimer’s dementia,” said Craft. “These findings show that we can now validate whether treatments are actually reaching their intended brain targets, which is critical information for designing successful trials.”

The imaging protocol used a precision nasal delivery system supplied by Aptar Pharma and could be adapted for other intranasal therapies targeting neurological disorders.

“The results of the study represent a significant step forward in medicine as they validate that our nasal delivery system was effective in delivering intranasal insulin safely and effectively to specific regions of the brain,” said Reenal Gandhi, director of business development for Aptar Pharma.

“As scientific understanding and development advance, we see continued opportunities for intranasal delivery to improve how therapeutics are delivered to the central nervous system.”

The Wake Forest University School of Medicine team is now planning larger validation studies within the next 12–18 months to explore how vascular health, amyloid accumulation and sex differences influence brain insulin delivery.

“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,” Craft said. “This is promising news for developing more effective and accessible treatments for Alzheimer’s disease.”