PET Imaging Validates Direct Brain Delivery of Intranasal Insulin in Alzheimer Disease: Daily Dose

_{©New Africa/AdobeStock}

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On August 11, 2025, we reported on a study published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions that evaluated the kinetics of insulin uptake and distribution in the brain.

The study

The first-in-human positron emission tomography (PET) study enrolled 16 older adults (mean age 72 years), including 7 cognitively unimpaired individuals and 9 diagnosed with mild cognitive impairment (MCI). Following administration of a novel radiolabeled insulin tracer, [68Ga]Ga-NOTA-insulin, using a precision 6-spray nasal delivery system, participants underwent a 40-minute dynamic brain PET scan followed by a 15-minute whole-body scan. All participants reported good tolerability and no difficulty with administering the nasal spray.

The findings

Investigators reported findings from quantitative analysis that showed elevated tracer uptake in brain regions integral to memory and cognition—specifically the hippocampus, olfactory cortex, amygdala, and temporal lobe. Notably, cognitively normal subjects exhibited higher and more sustained insulin uptake compared with MCI participants, who showed rapid initial accumulation followed by accelerated clearance.

Of further interest, results showed that in women, insulin uptake correlated positively with cardiovascular health biomarkers, while elevated ptau217, a phosphorylated tau isoform linked to amyloid pathology, correlated inversely with brain insulin absorption across multiple regions. Only 2 participants reported adverse events in the form of mild transient headaches reported.

Authors' comments

"Future studies should incorporate such validation before initiating clinical trials of intranasally administered agents. Further investigation of mechanisms underlying differences in INI uptake among clinical subgroups is also needed."

Click here for more details.