Alzheimer's Researchers Receive NIH Grant to Test Intranasal Insulin Spray

Researchers will receive $7.9 million over the next 5 years to test the effects of intranasal insulin therapy on patients with mild cognitive impairment and mild to moderate Alzheimer's disease.

Researchers will receive $7.9 million over the next 5 years to test the effects of intranasal insulin therapy on patients with mild cognitive impairment and mild to moderate Alzheimer’s disease.

Normalizing brain insulin in patients with mild cognitive impairment (MCI) and mild to moderate Alzheimer’s disease (AD) may improve memory, cognition, and daily functioning, according to a 4-month pilot trial entitled SNIFF-120 (Study of Nasal Insulin to Fight Forgetfulness). The study was conducted by researchers at the University of Washington and funded by the National Institute on Aging.

Previous research has shown that patients who have AD have reduced levels of insulin in the brain as well as resistance to the effects of insulin as AD progresses. Insulin resistance causes beta-amyloid accumulation outside the cell membrane, and scientists believe that beta-amyloid may be responsible for memory loss in AD. “A memory is simply a pattern of connections between neurons,” said Suzanne Craft, PhD, of the University of Washington and Veterans Affairs Puget Sound, in the HBO documentary film, The Alzheimer’s Project. “Anything that affects or modulates the connections of synapses is going to play an important role in memory.”

Dr. Craft and her co-investigators sought to determine how insulin abnormalities contribute to cognitive and brain changes associated with AD. They administered either a saline placebo or insulin nasal spray therapy with a nebulizer to 104 participants and measured cognition, memory, and functional performance in both groups at baseline, 2 months, and 4 months. Final patient outcomes were measured through cognitive (ADAS-Cog, delayed story recall) and functional (ADCS-ADL, Dementia Severity Rating Scale) tests. A small subset received brain scans using fluorodeoxyglucose positron emission tomography to measure glucose utilization, and spinal taps to check cerebrospinal fluid (CSF) biomarkers.

The researchers concluded that the insulin-treated participants showed net improvement on the functional tests, did not demonstrate decline on the cognitive tests, and had lower AD risk compared with participants taking placebo. The insulin treatment also appeared to protect patients from decreases in glucose utilization and actually improved glucose metabolism for some patients.

“Although we achieved statistical significance for most cognitive and functional outcome measures, the observed effects were small in absolute terms, as might be expected from this relatively brief intervention, and thus their long-term clinical significance is unclear,” noted the study authors.

Now, thanks to a new National Institutes of Health grant, Dr. Craft and her colleagues have the necessary funding to conduct a larger Phase 3 trial using similar experimental techniques as in the SNIFF-120 trial. She and her colleagues, in collaboration with the Alzheimer’s Disease Cooperative Study Consortium, will recruit 240 volunteers for a year-long study to further analyze how long-acting insulin affects cognitive function in MCI and AD patients. In addition, the investigators will attempt to measure the biomarkers associated with AD in CSF, measure brain blood flow, and use imaging tools to measure brain atrophy in all patients at the conclusion of the trial.