In case you hear the phrase Ozempic, weight reduction instantly involves thoughts. The drug—a part of a household of therapies known as GLP-1 agonists—took the medical world (and web) by storm for serving to individuals handle diabetes, decrease the danger of coronary heart illness, and quickly shed weight.
The medicine may additionally defend the mind towards dementia. In a medical trial together with over 200 individuals with gentle Alzheimer’s illness, a every day injection of a GLP-1 drug for one yr slowed cognitive decline. When challenged with a battery of assessments assessing reminiscence, language abilities, and decision-making, members who took the drug remained sharper for longer than those that took a placebo—an injection that appeared the identical however wasn’t practical.
The outcomes are the newest from the Evaluating Liraglutide in Alzheimer’s Illness (ELAD) research led by Dr. Paul Edison at Imperial School London. Launched in 2014, the research was primarily based on years of analysis in mice displaying liraglutide—a GLP-1 drug already accredited for weight reduction and diabetes administration in america—additionally protects the mind.
In Alzheimer’s illness, neurons die off and the mind steadily loses quantity. Within the trial, Liraglutide slowed the method down, leading to roughly 50 p.c much less quantity misplaced in a number of areas of the mind associated to reminiscence in comparison with a placebo.
“We’re in an period of unprecedented promise, with new therapies in varied phases of growth that gradual or could presumably forestall cognitive decline because of Alzheimer’s illness,” stated Dr. Maria C. Carrillo, Alzheimer’s Affiliation chief science officer and medical affairs lead, in a press launch. “This analysis offers hope that extra choices for altering the course of the illness are on the horizon.”
The outcomes have been introduced final month on the Alzheimer’s Affiliation Worldwide Convention.
Again to Fundamentals
The search for an Alzheimer’s illness therapy is suffering from failures. Most therapies purpose to deal with poisonous protein clumps that construct up contained in the mind. It’s thought that breaking them up might forestall neurons from withering away.
Just a few have had restricted success. Final month, the US Meals and Drug Administration (FDA) accredited a drug that breaks down the clumps in individuals already experiencing signs at an early stage of the illness. Just a few weeks later, the European Medicines Company refused to approve one other drug that additionally targets the clumps, saying the consequences of delaying cognitive decline didn’t stability the danger of great negative effects, together with mind swelling and bleeding.
Different scientists have appeared elsewhere—particularly, diabetes. Insulin helps preserve mind well being, and Kind 2 diabetes is a danger issue for growing Alzheimer’s illness. Reasonably than immediately breaking down protein clumps within the mind, would possibly we defend the mind by tweaking the physique’s metabolism?
Enter GLP-1 medicine. These mimic hormones launched by the abdomen after a satisfying meal, tricking the mind into pondering you’re full. In different phrases, the medicine don’t solely affect the intestine—in addition they change mind features.
In a mouse mannequin of Alzheimer’s, every day injections of liraglutide for eight weeks prevented reminiscence issues. Their neurons additionally thrived. Synapses—the junctions connecting mind cells—have been nonetheless in a position to quickly kind neural networks in areas particularly broken by the illness. Surprisingly, poisonous protein clumps additionally declined by as much as 50 p.c, and irritation dropped.
Liraglutide didn’t simply work on neurons. One other research, additionally in an Alzheimer’s mouse mannequin, discovered it quickly tweaked the metabolism of a specific sort of star-shaped mind cell that helps neurons. These cells don’t kind neural networks, however they do assist present vitality. In Alzheimer’s, they cease functioning usually, however liraglutide reversed the decline. In mice, the drug improved the cells’ capacity to help neurons, permitting the neurons to flourish and hook up with others. The mind additionally made higher use of sugar—its main gasoline—permitting it to present beginning to new neurons in a area essential for reminiscence.
However as the sphere frustratingly is aware of, mice are usually not individuals. Many promising therapies in mice have failed in medical research, incomes these endeavors the nickname “graveyard of goals.”
The Trial
Edison took on the duty of extending the analysis from mice to people. In 2019, he and his colleagues detailed plans for a medical trial to gauge liraglutide’s results in individuals with gentle Alzheimer’s. Known as ELAD, the research was to be randomized and double-blind—the gold normal in medical trials. Right here, neither physician nor affected person is aware of who’s getting liraglutide or the placebo.
They recruited 204 individuals to obtain injections, both liraglutide or placebo, on daily basis for a yr. Earlier than the trial, every individual had an MRI scan to map their mind’s construction and quantity. Different scans recorded mind metabolism, and a battery of reminiscence assessments detailed cognition. These assessments have been repeated on the finish, with security checkups in between, in case of negative effects.
The research had a number of targets. One was to see if liraglutide elevated the mind’s metabolism in areas closely impacted by Alzheimer’s—these associated to studying, reminiscence, and decision-making. One other examined mind quantity, which decreases because the illness progresses. The final evaluated cognitive assessments of reminiscence, comprehension, language, and spatial navigation.
Individuals who took liraglutide had practically 50 p.c much less mind quantity loss, particularly in areas related to reasoning and studying. “The slower lack of mind quantity suggests liraglutide protects the mind, very like statins defend the center,” stated Dr. Edison.
Liraglutide additionally boosted cognition. Evaluating scores from earlier than the trial, at its midpoint, and on the finish, those that acquired the drug had an 18 p.c slower decline than those that took the placebo. Nevertheless, the drug didn’t have an effect on mind metabolism.
Negative effects have been comparatively gentle. The commonest was nausea. Extra critical ones, not specified, occurred in 18 sufferers however weren’t doubtless associated to the therapy based on Edison.
To be clear, the group introduced the outcomes at a convention, they usually haven’t but been formally vetted by different consultants within the discipline. However they add to accumulating proof that GLP-1 medicine gradual cognitive decline. A Swedish research in June carried out a simulated trial in individuals with Kind 2 diabetes given GLP-1 or two different varieties of medicine and assessed their cognition afterward. Utilizing well being knowledge data from over 88,000 members adopted over 4 years, GLP-1 medicine have been higher than the 2 different diabetes medicine at protecting the danger of dementia at bay.
We don’t but understand how liraglutide protects the mind. Based mostly on research in mice, it doubtless works a number of methods, corresponding to decreasing irritation, clearing poisonous protein clumps, and enhancing talk between neurons, Edison stated.
However the thought is gaining steam. EVOKE Plus, a late stage medical trial of semaglutide—the chemical in Ozempic—is ongoing. The research will take about three and a half years, with an estimated enrollment of 1,840 individuals with early Alzheimer’s illness. It’s set to conclude in late 2026.
“Repurposing medicine already accredited for different circumstances has the benefit of offering knowledge and expertise from earlier analysis and sensible use—so we already know quite a bit about real-world effectiveness in different ailments and negative effects,” stated Carrillo.
Picture Credit score: Maxim Berg / Unsplash
