Trial finds insulin nasal spray may slow age-related cognitive decline
The results of a small Phase 2 clinical trial offers promising signs that daily doses of an insulin nasal spray could be used to slow age-related cognitive decline. The trial found the treatment to be effective in elderly subjects both with and without type 2 diabetes.
Over the last couple of decades an intriguing hypothesis has emerged suggesting insulin resistance in the brain may play a role in age-related cognitive and functional decline. To combat this aspect of the aging process some researchers have hypothesized intranasal delivery of insulin could be an effective tool for maintaining brain health in our senior years.
The idea is that nasal delivery of insulin sends the hormone directly to the brain. This means intranasal insulin (INI) wouldn’t be a replacement for insulin therapy in diabetics, but instead it works to modulate insulin signaling in the brain.
Prior human trials with intranasal insulin have delivered mixed results. A moderately sized trial testing the treatment for 12 months in patients with either Alzheimer’s or mild cognitive impairment found no benefits. However, this new research hypothesized the treatment could be more effective in preventing general age-related cognitive decline instead of acute dementia.
The trial recruited 223 adults, aged between 50 and 85, with around half the cohort diagnosed with type 2 diabetes. The participants were divided into four groups: a diabetes group given placebo, a diabetes group given intranasal insulin, a healthy group given placebo and a healthy group given intranasal insulin. For 24 weeks the participants sprayed 40 IU (0.4 ml) of human insulin or placebo intranasally before breakfast.
At the beginning of the trial participants completed a variety of cognitive and mood tests. The research also tracked participants’ gait speed, as prior studies have consistently found the pace at which a person walks can be used to determine their neurological health.
“Walking speed is an important clinical predictor of well-being in the elderly that correlates with cognitive decline, hospitalizations, disability and death,” explained Vera Novak, corresponding author from Harvard Medical School. “At baseline, participants with diabetes walked slower and had worse cognition than the participants without diabetes, who served as a clinical reference for normal aging population.”
At the end of the study period the researchers found those diabetics who were taking the intranasal insulin improved their gait speed and performed better on cognitive tests than those diabetics in the placebo group. The non-diabetic group receiving the intranasal insulin also displayed improvements on decision making and verbal memory tests compared to non-diabetics in the placebo group.
The biggest improvements in the non-diabetic group were seen in those subjects who started the trial in a prediabetic state. This suggests the treatment may be most effective at slowing cognitive decline in either diabetics or those with prediabetes.
“The consistency of the trends in the data showing better performance on walking speed and cognition for INI-treated participants, especially in those with pre-diabetes, carries great implication for potential early intervention using INI in this population to prevent or slow down the progression toward Alzheimer Disease’s related dementias,” noted senior author Long Ngo.
From a safety perspective the researchers found intranasal insulin generated no adverse effects after 24 weeks. Also of note, intranasal insulin did not affect or disrupt subcutaneous insulin treatment in those type 2 diabetic subjects receiving ongoing glucose-lowering therapy.
The results are certainly fascinating but the researchers are cautious to stress there are still lots of questions to answer before some kind of intranasal insulin spray for brain health is available to the elderly. This proof-of-concept trial does offer strong preliminary safety and efficacy evidence but it's still unclear what the optimal dose for intranasal insulin may be, or whether it is safe to administer over very long periods of time.
“INI-treated diabetic participants had faster walking speed, increased cerebral blood flow and less insulin resistance, while INI-treated controls performed better on executive function and verbal memory tasks,” the researchers concluded in the new study. “Overall, INI effect demonstrated improvements of walking speed, executive function and verbal memory. These findings are clinically relevant and warrant further investigation in a larger clinical trial.”
The new study was published in the Journal of Neurology.