Sprayed Insulin into the Nose—and Memory Improved? [Professor Ahn Cheol-woo's Encyclopedia of Hormones]

[Financial News]Hormones have evolved and been passed from one species to another alongside the evolution of life. If there is a chemical substance that must exist as long as life exists, it is hormones. In this sense, hormones are immortal. Through this column, Professor Ahn Cheol-woo aims to explain hormones—the chemical substances that govern the body—accurately and suggest ways to live healthier and happier lives.
The claim that Alzheimer's disease (AD) should be called type 3 diabetes emerged from evidence that insulin plays a decisive role in the formation of amyloid plaques and the hyperphosphorylation of tau protein, suggesting that insulin may act directly on brain cells and cause AD.
If insulin resistance in the body is type 2 diabetes, then insulin resistance in the brain is type 3 diabetes. The case for calling this disease type 3 diabetes is based on several observations: AD begins when the supply of glucose to brain cells becomes impaired; insulin levels in the brain are normal, but insulin does not respond to its receptors; and the supply of other neurotransmitters declines along with insulin resistance.
An even stronger basis for this theory may be the fact that insulin is involved in cognition in the brain. Insulin is known to reach the brain through routes such as the blood-brain barrier and the blood-cerebrospinal fluid barrier, where it helps control appetite along with leptin, Ghrelin and Dopamine.
In 1999, however, researchers discovered that insulin is involved in the secretion of acetylcholine (ACh) and norepinephrine in the brain. These two substances are well known for enhancing cognitive function. A 2001 study found that insulin acts on brain cell membranes and promotes the expression of N-methyl-D-aspartate, a receptor for glutamate, thereby contributing to memory formation. Since then, a steady stream of studies has examined the relationship between insulin and cognition.
A 2002 paper suggested that insulin may help increase glucose metabolism in the cerebral cortex. Another theory proposed that insulin may contribute to glucose metabolism by distributing glucose transporters to the locations where they are needed according to type. The academic community now appears to be embracing the concept that dementia is diabetes occurring in the brain—in other words, insulin resistance in the brain.
Most importantly, clinical studies have actually found that administering insulin to the brain improves cognitive function. In 2004, a research team from the Department of Neuroendocrinology at the University of Lübeck administered insulin nasally to 38 healthy men and women for eight weeks and tested changes in their cognitive abilities. The results showed improvements in word memory and attention, as well as better moods, including greater self-confidence.
In 2011, a U.S. research team conducted a similar experiment with patients with mild-to-moderate AD. The results showed that the patients' ability to perform daily activities also improved considerably. No changes in cognitive function were observed among patients who inhaled a placebo.
In 2022, a research team at Beth Israel Deaconess Medical Center, affiliated with Harvard Medical School, administered insulin through the nose every day for 24 weeks to a total of 174 people and analyzed their cognitive abilities and gait. The group of diabetic patients who received insulin performed simple tasks and multitasking faster than the diabetic group that received a placebo.
Among participants without diabetes, those who received insulin also performed tasks better and had stronger verbal memory than those who received a placebo. Magnetic resonance imaging showed increased blood flow in the frontal cortex among diabetic patients who received insulin. Regardless of whether they had diabetes, participants who received insulin walked faster.
Across all of these clinical trials, the nasal insulin spray neither raised nor lowered participants' blood glucose levels, and it caused no other side effects. However, some people experienced no effects, while others experienced only limited benefits. The nasal insulin spray for treating AD remains in the trial stage.
If the treatment proves highly effective and safe enough for widespread prescription, it could usher in a new era in dementia treatment. Applying it particularly to early-stage dementia, when cognitive impairment is not yet severe, could significantly slow the progression of the disease and enable patients to spend their remaining time more meaningfully.
/Ahn Cheol-woo, Professor of Endocrinology, Gangnam Severance Hospital
[email protected] Jung Myung-jin, Medical Correspondent Reporter