Intranasal Insulin Spray Improves Cognitive Function

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intranasal spray
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According to a phase 2 trial, an intranasal insulin spray can potentially help treat cognitive decline in elderly diabetics.

A team of researchers at Beth Israel Deaconess Medical Center (BIDMC) conducted a trial assessing the long-term effects of intranasal insulin spray on cognition and gait in people with and without diabetics. They published their findings in the Journal of Neurology.

Called MemAID, the trial recruited more than 200 participants aged 50-85 years of age. Both diabetics and non-diabetics were part of the trial. Prior to the trial, researchers conducted various cognitive and mood tests on the participants. These helped assess their normal and dual-task walking speeds, attention, memory and executive function, and mood.

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.

Dr. Vera Novak, study author

Both the diabetics and healthy individuals were further divided into a placebo group and another that received the insulin spray. An electronic atomizer helped deliver a daily dose of 0.4ml of insulin intranasally. The placebo spray was also delivered intranasally. Participants received the treatment for a total of 24 weeks. The researchers further conducted MRI scans to evaluate the effect of intranasal insulin on cerebral blood flow.

According to the results, the treatment did not cause any moderate or serious adverse events among the participants. Moreover, it was safe even in type 2 diabetics undergoing treatment with subcutaneous insulin injections.

The results further revealed an improved cerebral blood flow and walking speed among diabetic patients treated with insulin spray. Whereas in those with pre-diabetes, the spray improved decision making and verbal memory. Therefore, the study authors suggest that intranasal insulin is investigated as a possible treatment for age-related cognitive decline in type 2 diabetics.

The Link Between Diabetes and Cognitive Decline

The World Health Organization (WHO) estimates that more than 90% of people with diabetes have type 2 diabetes. People with type 2 diabetes suffer from insulin resistance; thus, the body is unable to respond to insulin, causing an increase in blood glucose levels. Along with energy metabolism, insulin also plays a role in brain signalling. Typically, insulin helps the muscles, liver, and fat cells to take up glucose and produce energy. The extra glucose in the bloodstream is converted and stored into fat to provide energy in times of low glucose levels. Thus, the hormone helps maintain blood glucose levels within the normal range.

Therefore, impaired insulin signalling in diabetes increases the risk of cognitive decline and dementia in adults. Previous studies have shown intranasal insulin as effective at improving verbal memory and as a potential treatment for cognitive decline in the elderly.

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.

study authors

According to the study author, Dr. Vera Novak, walking speed is a good clinical predictor of cognitive decline, hospitalizations, disability, and death in the elderly. In the clinical trial, both diabetics and healthy individuals had faster walking speeds and better executive functioning and memory. Furthermore, compared to the control group, researchers noted lower plasma insulin and insulin resistance in diabetics treated with intranasal spray. Thus, resulting in an improvement in cognition and gait among the participants.

The study authors believe that the trial’s findings warrant a larger trial that can further confirm the beneficial effect of intranasal insulin.

How Does the Insulin Spray Work?

Insulin is naturally produced by the pancreas in our bodies. However, in certain conditions such as type 1 diabetes, the pancreas is unable to produce insulin. In other instances, the body’s cells develop a resistance to insulin and are unable to use it, such as type 2 diabetes. Thus, resulting in increased blood sugar levels.

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 (intranasal insulin) in this population to prevent or slow down the progression toward Alzheimer Disease’s related dementias.

Dr. Long Ngo, senior study author

Insulin has several functions in the brain. The hormone helps regulate neuronal signalling, growth, metabolism, and survival of neuronal cells within the brain. Furthermore, increased brain insulin levels improve learning and memory in individuals. Therefore, impaired insulin levels and insulin resistance affects brain functioning as well.

An intranasal spray helps transport insulin directly to the central nervous system (CNS) via the olfactory, trigeminal pathways and perivascular channels. Moreover, it bypasses the blood-brain barrier, preventing any systemic side effects. Once inside, it binds to receptors in regions involved in memory and cognition such as the hypothalamus, hippocampus, cerebellum, and substantia nigra. Along with enhanced brain metabolism, insulin also increases the perfusion of the regions.

Since gait is linked to brain hypoperfusion, the improved brain perfusion also causes improvement in gait and walking speeds among participants. The study is, therefore, a proof-of-concept for the safety and efficacy of intranasal spray for treating cognitive decline and gait in elderly diabetics.

Reference:

Vera Novak et al, MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial, Journal of Neurology (2022). DOI: 10.1007/s00415-022-11119-6

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