Using advanced single-nuclei RNA sequencing (snRNA-seq) and a widely used preclinical model for Alzheimer’s disease, researchers from Mass General Brigham and collaborators at SUNY Upstate Medical University have identified specific brain cell types that responded most to exercise. These findings, which were validated in samples from people, shed light on the connection between exercise and brain health and point to future drug targets. Results are published in Nature Neuroscience.

“While we’ve long known that exercise helps protect the brain, we didn’t fully understand which cells were responsible or how it worked at a molecular level,” said senior author Christiane D. Wrann, DVM, PhD, a neuroscientist and leader of the Program in Neuroprotection in Exercise at the Mass General Brigham Heart and Vascular Institute and the McCance Center for Brain Health at Massachusetts General Hospital. “Now, we have a detailed map of how exercise impacts each major cell type in the memory center of the brain in Alzheimer’s disease.”

The study focused on a part of the hippocampus-a critical region for memory and learning that is damaged early in Alzheimer’s disease. The research team leveraged single-nuclei RNA sequencing, a relatively new technologies that allow researchers to look at activity at the molecular level in single cells for an in-depth understanding of diseases like Alzheimer’s.

The researchers exercised a common mouse model for Alzheimer’s disease using running wheels, which improved their memory compared to the sedentary counterparts. They then analyzed gene activity across thousands of individual brain cells, finding that exercise changed activity both in microglia, a disease-associated population of brain cells, and in a specific type of neurovascular-associated astrocyte (NVA), newly discovered by the team, which are cells associated with blood vessels in the brain. Furthermore, the scientist identified the metabolic gene Atpif1 as an important regulator to create new neurons in the brain. “That we were able to modulate newborn neurons using our new target genes set underscores the promise our study,” said lead author Joana Da Rocha, PhD, a postdoctoral fellow working in Dr. Wrann’s lab.

To ensure the findings were relevant to humans, the team validated their discoveries in a large dataset of human Alzheimer’s brain tissue, finding striking similarities.

This work not only sheds light on how exercise benefits the brain but also uncovers potential cell-specific targets for future Alzheimer’s therapies. Our study offers a valuable resource for the scientific community investigating Alzheimer’s prevention and treatment.” Nathan Tucker, biostatistician at SUNY Upstate Medical University and co-senior of the study

In 1935, in the labs of Cornell University, a discovery was made that should have taken the world by storm.

It was all thanks to Prof Clive McCay, an American nutritionist, and a group of rats. Or rather, several groups of rats – McCay had split the rodents up, allowing some to eat as much as they wanted while the others lived on substantially reduced rations.

After 30 months, all the rats that were allowed to eat what they liked had died. But just under half of the animals on the restricted diet were still going strong. In fact, by the end of the experiment, McCay found that the carefully restricted diet almost doubled the average lifespan of a rat.

You might worry that the calorie-counting animals were doddering along, unable to summon the energy even to die long after their well-fed brethren had copped it. This wasn’t the case: the restricted diet rats were also healthier. They mostly evaded cancer, had fewer lung and kidney problems and even had silkier fur.

Overall, McCay’s findings suggested it might be possible to influence the ageing process through diet – that what you eat could effectively slow your ageing on a biological level.

This absolutely remarkable finding didn’t really go anywhere for decades – perhaps because US life expectancy at the time was just 60 years. Fewer people would have been concerned with ageing well, simply because far fewer of them could look forward to ageing at all.

Fortunately for us, this area of science has seen a resurgence of interest in recent years. Results similar to McCay’s have now been seen in other animals, from worms and flies to trout and dogs.

Prof Clive McCay’s experiments in the 1930s lead to some startling findings regarding nutrition and lifespan in rats. – Photo credit: Cornell University Faculty Biographical Files/Division of Rare and Manuscript Collections/Cornell University Library

We can also now study mice on restricted diets and see that their ageing is indeed slowing down by looking at the ticking of their ‘epigenetic clocks’ (a popular method of measuring biological age) or the shortening of their telomeres (the protective caps on the ends of DNA that shorten as a living organism gets older).

Something similar may well apply to humans. In fact, some scientists estimate that switching from a typical US or UK diet to an ‘optimal’ diet could add anything from a few years to a decade to life expectancy.

All of this means that we’ve got pretty compelling evidence that what we eat can have an effect on the ageing process. It may be possible, in other words, to eat smarter and live longer as a result.

But rats and trout aren’t human beings, and the simple measures that could help them live longer won’t necessarily work for us. So what will?

There’s a lot of conflicting research out there and plenty of potentially damaging fad diets. But there are some ways of eating that have repeatedly been shown to give you the best chance of living a longer and healthier life.

1. Get the chemistry right

In 1677, Dutch biologist and microscopy pioneer Antonie van Leeuwenhoek was looking for more things to examine using his new magnifying device and was persuaded by Secretary of the Royal Society Henry Oldenburg to try semen. His first discovery was the sperm cell – though he called them ‘animalcules’ and their true function wouldn’t be uncovered for almost two centuries.

He also noticed that, as the semen was drying out, tiny crystals began to form. These crystals were later dubbed ‘spermidine’ and we now think that spermidine might have anti-ageing properties. Why? Because it activates a process known as autophagy, whereby cells scavenge old, faulty components for spare parts, giving themselves an anti-ageing spring clean in the process.

Despite the name, and the history behind its discovery, spermidine is a chemical that’s actually found throughout the natural world, not just in semen: foods particularly rich in it include soybeans, mushrooms and cheddar cheese.

Experiments in mice show that adding the compound to their water can make them live longer and people who get the most spermidine in their diets have been shown to live up to five years longer on average than those who consume the least.

Cheddar cheese and mushrooms are good sources of spermidine. – Photo credit: Science Photo Library

There are other natural molecules found in foods that could have anti-ageing properties. Curcumin, one of the chemicals that gives turmeric its yellow colour, may have anti-inflammatory effects and is being investigated as a possible adjunct to cancer treatment.

Similarly, quercetin (found in various foods including elderberries, red cabbage and dark chocolate) and fisetin (found in fruits such as strawberries) are both ‘flavonoids’ that have been found to clear out ‘old’ cells in mice.

A word of caution here: there’s no such thing as a ‘superfood’, and singling out this, that or the other magic molecule as a health-giving elixir that means we should all binge on a particular kind of berry is bad, reductive science. That said, there’s probably no harm in munching on a few extra mushrooms or red cabbage leaves.

2. Eat more vegetables

The biggest takeaway from two major studies into how changes in diet affect life expectancy was that we should eat more vegetables and plant-based foods. Specifically, eating more whole grains (like wholemeal bread or brown rice, as opposed to the ‘refined’ white alternatives), legumes (peas, beans and pulses) and nuts could add a few more years to your life expectancy.

Additionally, the researchers found that eating too much red and processed meat could have a negative impact, as could drinking too many sugar-sweetened beverages. In fact, moving from the current average consumption of meat and sugary drinks to the optimal level could add three years to your life expectancy.

And what is the optimal level of processed meat and sugary drinks? According to both studies, none at all.

Vegetables – and legumes especially – provide clear health benefits. – Photo credit: Getty Images

You can take all these findings with a tiny pinch of salt, however – especially as excessive sodium chloride consumption is associated with premature death. That’s because the biggest and best studies of long-term health and lifespan face a big challenge: they’re observational.

This means they simply ask people what they eat and follow them for decades to see how long they live. As a result, other factors about participants’ lives could be overlooked.

For instance, such studies show that vegetarians live longer, but is that because vegetables are healthier than meat or because veggies and vegans are likely to be more health-conscious in other ways?

The gold standard would be randomised trials that split people into several diet groups, but to avoid being too expensive (and unethical), experiments of this kind generally only take place over a few weeks or months, rather than years.

The studies of this sort that have been undertaken so far do back up the big observational studies in terms of short-term markers of health, such as improvements in blood tests. And again, one systematic review found that the best foods for improving blood markers were nuts, legumes and whole grains, while the worst were red meat and sugar-sweetened beverages.

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3. Pay attention to your source of protein

Thanks to studies carried out on various animals – including on worms and flies – scientists have found that restricting protein intake could be the key to a longer life in animals.

In humans, though, the evidence requires a closer look. One major study in 2014 suggested that people eating less protein lived longer than those with a high-protein diet: a 50-year-old eating less than 45g of protein per day could expect to live to 82, while one eating 90g per day would only make it to 78.

This could be because high-protein diets increase levels of a pro-growth hormone called IGF-1, which, as well as building muscle, is also known to accelerate the ageing process and could increase the risk of cancer.

Protein is important, but the foods you get it from are just as important. – Photo credit: Getty Images

There are a couple of issues with this theory, however. Firstly, after the age of 65 or so, the effect reversed, and those eating more protein lived longer than those eating less. This is perhaps because protein helps us with the vital task of maintaining muscle mass as we get older.

Secondly, when the authors examined animal and plant protein separately, the effect in middle age disappeared. So perhaps it’s the other ingredients found in meat (especially red and processed meat) that cause the increased risk of cancer and death, rather than the protein itself.

Indeed, a huge review of 32 studies looking at protein consumption found that higher protein consumption decreases risk of death overall – although a diet that substitutes plant protein (think nuts, seeds, legumes and soy products) for meat protein could be associated with longevity.

4. Reduce visceral fat

We’ve all been told countless times that we should try to maintain a healthy weight. Looking at the biology of ageing, though, really underscores why this is so important.

For one thing, it’s estimated that every extra five body mass index (BMI) points could knock a few years off your life expectancy. It’s hard to give precise estimates, not least because BMI is an imperfect metric – it can’t tell the difference between fat and muscle. But there is an explanation for this statistic.

Watching your waistline is a good way to keep yourself healthier for longer. – Photo credit: Getty Images

We now know that fat – and particularly ‘visceral’ fat, which builds up between the organs inside your body, as opposed to the ‘subcutaneous’ fat that accumulates under your skin – emits a cocktail of inflammatory molecules that can speed up the ageing process.

Chronic inflammation is both a cause and consequence of ageing, so being overweight is a little like ageing at an accelerated rate. This means that being overweight increases the risk of many different diseases that become more common as we get older, from heart disease and diabetes to some kinds of cancer.

It can, of course, be pretty challenging to lose weight and visceral fat, but the good news is that there doesn’t seem to be a single ‘best’ diet when it comes to doing so.

Studies pitting various weight-loss diets against one another (low-fat vs low-carb, for instance) have found that, as long as you eat less, it doesn’t matter exactly what it is. Find something that’s healthy and works for you, rather than worrying about what the perfect weight-loss diet might be.

5. Not so fast with the fasting

While touted as an anti-ageing miracle by many online influencers, the evidence for the benefits of fasting is hardly clear-cut. Studies on smaller animals (such as McCay’s) appear to show that cutting the calorie intake of animals can lengthen their lifespan. But, as we’ve already noted, humans aren’t just big mice – so does the same necessarily apply to us?

In fact, when calorie restriction was tried on rhesus monkeys, which are far closer to us than rats in both evolutionary and lifespan terms, the effects were much weaker. The monkeys eating less showed a decent extension of ‘healthspan’ – the length of life spent in good health – but didn’t seem to live much longer if already eating a basically healthy diet.

The handful of studies carried out in actual humans have been too short to give a clear answer. A couple of years’ dietary restriction in people resulted in improved blood test results, but also side effects ranging from anaemia (where a deficiency of red blood cells leaves your tissues short of oxygen) and loss of sex drive to irritability and feeling cold.

The final piece of bad news? That hunger you feel when restricting your diet will never go away. As anti-ageing scientists joke, while dietary restriction probably won’t make you live longer, it will certainly feel like it.

The evidence for the benefits of intermittent fasting and similar regimes is by no means conclusive. – Photo credit: Getty Images

But what about intermittent fasting? What if we could get some of the benefits of eating less all the time, but without the constant hunger? The theory is that not having enough protein coming in promotes autophagy, the cellular recycling and repair process.

Could we activate such mechanisms by not eating at all for a period of time, but without cutting back on calories overall?

In short, probably not.

The evidence is similarly thin whether we look at time-restricted feeding (where you only eat in a certain window during the day, often six or eight hours – one way you can achieve this is by skipping breakfast), the 5:2 diet (where you eat nothing or a substantially reduced amount on two non-consecutive days a week) or even periodic fasting (whose adherents consume only water for five-plus days every few months).

While intermittent fasting can be an effective weight-loss strategy in the short term, there is a hidden pitfall: studies show that people who fast can lose a greater percentage of muscle mass than people adhering to a consistent low-calorie diet. Since strong muscles are critical for health while ageing, this is potentially a red flag.

6. Give diet pills a miss… for now

Despite the claims you might see on social media, there’s no pill or supplement with outstanding anti-ageing properties that has been extensively tested on humans. There are several exciting prospects in the pipeline, however.

One such is rapamycin, a drug currently used for organ transplant patients that makes mice live 10 per cent longer, even if started at an older age. It does so by activating autophagy, the same cellular repair and recycling process seen when cutting back on food.

Rapamycin was intended to help transplant patients, but research suggests it may also have life-extending side-effects. – Photo credit: Getty Images

Then there’s semaglutide (also known by its trade names Ozempic and Wegovy). While it’s currently used by humans to curb appetite, it’s also been shown to reduce the risk of cardiovascular disease in old age. Yet whether these effects are health-improving, anti-ageing or just side-effects of the weight-loss it causes needs further investigation.

Even more treatments could be on the way. The lessons from dietarily restricted animals should allow us to bottle more of their biology, perhaps using drugs or gene therapy to turn back our biological clocks. Perhaps the greatest gift that ageing biology will give us – apart from longer, healthier lives, obviously – will be freedom from endless fad diets, and the dodgy doctors and health influencers peddling them.

For now, though, if you want to stay healthy enough for long enough to enjoy the anti-ageing drugs that are currently in development, adopting an anti-ageing diet is an excellent way to start.

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New research suggests weight-loss drugs could reduce the risk of dementia and stroke.

Experts also claim people with type 2 diabetes who are using the jabs may be less likely to die prematurely.

It’s believed around 1.5 million people currently take weight loss jabs, with many opting to self-inject semaglutide to ‘help manage weight’, said Dr Vijaya Surampudi, a physician nutrition specialist and assistant director of the UCLA Weight Management Program (RFO).

U.S Food and Drug Administration-approved drugs for chronic weight management include Wegovy and Zepbound.

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In 2017, Ozempic was approved by officials for treating type 2 diabetes only, despite some claiming to use it for weight-shedding purposes.

As weight loss jabs’ popularity rises, more and more scientists are dedicating their time to understanding how the injectable drugs can impact our health – and the results apparently could be pretty positive.

Weight-loss drugs could reduce dementia and stroke risk, according to a new study (Getty Stock)

In a newly published study, researchers from Taiwan examined 60,000 people from across the world with type 2 diabetes and obesity.

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Half of the study’s participants – who had an average age of 58 – were given GLP agonist drugs Wegovy and Mounjaro, while the remaining members of the sample were asked to use anti-diabetic medication.

Results, published in the journal JAMA Network Open, found that after seven years, people who had taken Wegovy and Mounjaro appeared to have a 37 percent lower risk of dementia than those on the anti-diabetic medication.

They also exhibited 19 percent reduced risk of stroke, as per the report.

According to the study’s authors, their follow-up findings suggested that weight-loss jabs offered ‘potential neuroprotective and cerebrovascular benefits beyond glycemic control, potentially improving long-term cognitive and survival outcomes in adults with type 2 diabetes and obesity’.

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However, the academics added that they would need to further study the subject to confirm their suspicions.

Academics have said further study is needed to confirm their findings (Getty Stock)

Speaking about the lowered dementia and stroke risks, Professor Tara Spires-Jones, director of the Centre for Discovery Brain Sciences at the University of Edinburgh and group leader in the UK Dementia Research Institute, said: “This is a very interesting study adding to evidence that GLP1 receptor agonists are associated with a lower risk of dementia in people with type 2 diabetes and obesity.

“This type of study cannot determine whether the drugs reduced disease risk by directly protecting the brain. It is highly likely that effectively treating type 2 diabetes and obesity would reduce dementia and stroke risk, as they are known risk factors for these conditions.

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“Further work is needed, including randomised clinical trials to confirm these drugs are protective in people with diabetes and obesity and other trials are needed to determine whether these drugs will be protective in people who do not have type 2 diabetes and obesity.”

How does type 2 diabetes increase dementia risk?

Dementia is intrinsically linked with type 2 diabetes sufferers (Getty Stock)

According to Alzheimers.org, people with diabetes are at an increased risk of developing dementia compared to those without diabetes.

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This is possibly because diabetes is linked to various other dementia risk factors, including high blood pressure, high cholesterol and obesity.

Some changes that occur in Alzheimer’s disease are similar to those in diabetes, the site stated.

This included nerve cells in the brain that become resistant to the effect of insulin, causing a build-up of amyloid and tau proteins in the brain.

Yhe National Institutes of Health (NIH) stated that type 2 diabetes is a ‘robust predictor of cognitive impairment and decline in older adults’, with multiple population-based studies reporting an association.

The findings were published in the Journal of Alzheimer’s Disease .

Xu is the lead author of a new study which found that semaglutide — the active ingredient in type 2 diabetes and weight-loss glucagon-like peptide-1 agonist ( GLP-1) medications Ozempic and Wegovy — may help lower dementia risk in people with type 2 diabetes.

“On the other hand, about 50% of dementia cases are preventable by targeting its 14 known modifiable risk factors. However, each risk factor contributes 1%-7% to the overall dementia risk. Therefore, we need prevention strategies that can simultaneously target multiple dementia risk factors,” Xu explained.

“Currently, there is no cure for dementia,” Rong Xu , PhD, professor of biomedical informatics and director of the Center for AI in Drug Discovery at Case Western Reserve University in Ohio, told Medical News Today.

Experts have identified several risk factors for dementia. Some are not changeable, such as age and genetics , while others are modifiable lifestyle factors.

There is currently no cure for dementia, which is an umbrella term for a group of brain disorders including Alzheimer’s disease , Lewy body dementia , and vascular dementia .

According to Alzheimer’s Disease International, as of 2020, there were over 55 million people living with dementia , with that number expected to rise to 78 million by 2030.

“In addition, semaglutide has anti-inflammatory effects, and inflammation plays a significant role in the development and progression of all-cause dementias,” she continued. “These suggest that semaglutide could be an effective pharmacological prevention strategy for dementia in high-risk populations such as patients with type 2 diabetes.”

“Semaglutide is highly effective in simultaneously targeting several dementia risk factors, including obesity, diabetes, and cardiovascular diseases , and appears to also be beneficial for [counteracting] smoking and alcohol drinking ,” Xu said.

In addition to semaglutide, scientists also looked at other type 2 diabetes medications, including insulin , metformin , and older generation GLP-1s.

Study participants were followed for three years to see if they developed any Alzheimer’s disease-related dementias (ADRD) . Types of ADRD included Lewy body dementia, vascular dementia, and frontotemporal dementia .

For this study, researchers analyzed electronic health record data from more than 1.7 million adults in the United States with type 2 diabetes.

“Economic and policy analyses are needed to examine the cost-effectiveness of integrating semaglutide and other pharmacotherapy-based prevention strategies with existing behavior-based approaches, such as exercise and diet in achieving substantial benefits for preserving cognitive function and preventing dementia,” Xu noted.

“Preclinical and clinical studies are necessary to understand the mechanisms and establish causal effects through randomized trials,” she continued.

For the next steps in this research, Xu said the team plans to examine if tirzepatide — the active ingredient in GLP-1 medications Zepbound and Mounjaro — or other emerging newer generation GLP-1s have similar or stronger effects on dementia, as well as monitoring long-term side effects.

“For people concerned about dementia, this information can guide informed decisions on choosing anti-diabetic medications for diabetes management while mitigating dementia development,” she added.

“Our findings show evidence that semaglutide treatment in patients with diabetes appears to protect from vascular dementia and other dementia, but not frontotemporal or Lewy body dementia,” Xu explained. “In addition, this is an associational study and no causation can be drawn.”

At the study’s conclusion, researchers found that participants taking semaglutide had a significantly lower risk of developing vascular dementia than those taking any other type 2 diabetes medication, including other GLP-1s.

Similarly, another study, published in JAMA Network Open in July 2025, also found evidence that users of semaglutide or tirzepatide had significantly lower risks of dementia, stroke, and all-cause mortality in adults with type 2 diabetes and obesity.

Comparing the effects of semaglutide and tirzepatide with other antidiabetic drugs, the cohort study of 60,860 patients indicated that GLP-1 agonists may have both neuroprotective and cerebrovascular benefits beyond managing blood sugar, and may potentially help improve long-term cognitive health.

MNT spoke with Mir Ali, MD, a board-certified general surgeon, bariatric surgeon, and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, to learn more about how semaglutide might help lower a person’s dementia risk.

“This class of medications are in widespread use and currently the most effective weight loss medications available,” Ali, who was not involved in the current study, explained. “Finding all the effects of these medications may expand possible indications for these drugs and possibly increase insurance coverage.”

Hypothesizing on potential mechanisms of prevention, Ali told us:

“To my knowledge the exact cause of Alzheimer’s dementia is unknown; obesity in general causes a chronic inflammatory process through the body and this can contribute to many medical issues. Perhaps the decrease in chronic inflammation may lead to reduction in dementia risk.”

MNT also spoke to Manisha Parulekar, MD, FACP, AGSF, CMD, director of the Division of Geriatrics at Hackensack University Medical Center, and co-director of the Center for Memory Loss and Brain Health at Hackensack University Medical Center in New Jersey, about the current research.

Parulekar, who was similarly not involved in this study, commented that people with 2 diabetes have a significantly increased risk of developing Alzheimer’s disease and other forms of dementia, and this research suggests a shared underlying mechanism or pathway.

“Additionally, GLP-1 receptor agonists (like semaglutide) have shown neuroprotective effects,” Parulekar continued. “Preclinical studies (in animals) have demonstrated that GLP-1 receptor agonists can protect neurons, reduce inflammation in the brain, and improve cognitive function.”

“Semaglutide also improves insulin sensitivity and glucose control, and also promotes weight loss. These improvements in metabolic health could indirectly reduce the risk of dementia. For example, better glucose control can reduce vascular damage, which is a contributing factor to vascular dementia. Weight loss can also improve cardiovascular health, which is linked to brain health.”

— Manisha Parulekar, MD, FACP, AGSF, CMD

She can see the difference. Yazhou Li, a neuroscientist at the National Institute of Aging in Bethesda, Maryland, studies the effects of different drugs on brain impairments including traumatic brain injury, Alzheimer’s disease, stroke, and Parkinson’s disease. Working in the laboratory of neuroscientist Nigel Greig, Li and her colleagues test drugs on injured​ cells in dishes, run mice and rats through mazes, look at their brains. They are trying to find out if treatment with certain drugs might reduce the devastating effects of dementia or brain injury.

And the latest drug they’re testing? Seems to work. The damage is “much more intense without treatment, and much more subdued with treatment,” Li says, though she cautions, “the animals aren’t, like, suddenly normal.” But after injury or in models of Alzheimer’s or Parkinson’s, mouse brains show less inflammation when the animals are given this drug. They move better and solve mazes faster than animals that don’t receive the treatment.

What’s surprising is the drug in question. Li has been dosing the mice with one of the GLP-1 agonist drugs—the ​​suddenly-everywhere class of drugs that includes Ozempic, Wegovy, and Mounjaro. Originally designed to treat diabetes and help with weight loss, GLP-1 (glucagon-like peptide 1) agonists are being tested against a number of diseases as scientists explore their wide-ranging effects—and pharmaceutical companies look to make even more profits from the burgeoning wonder drugs.

The drugs are currently in their silver bullet phase. No one doubts that they reduce insulin resistance, effectively treating ​t​​​ype 2 diabetes. But ​t​​ype 2 diabetes isn’t just an insulin or blood sugar disease—it has many other possible effects. One of them: a higher risk of dementia as patients age.

And as Li and a cohort of cognitive researchers are discovering, GLP-1 drugs might help reduce that risk. But how they work, how well they work, and who exactly will benefit from them are harder questions to answer.

Diabetes and dementia

Insulin is a vital molecule. After a person eats, beta cells in the pancreas release insulin into their blood. The hormone hits cells throughout the body, making them move glucose transporters to the cell membrane—opening the door for sugar to enter cells, which drives down glucose levels in the blood.

The brain, however, ​​is a sugar hound​, using as much as 20 percent of ​​the glucose ​we produce. Glucose transporters are always present on brain cells, keeping the doors permanently open to sugar. But this doesn’t mean insulin isn’t important for our brain.

In the brain, insulin is “more of a growth factor,” says Christian Hölscher, a neuroscientist at the Henan Academy of ​Innovations in ​Medical Sciences and chief scientific officer at Kariya Pharmaceuticals, a drug company developing GLP-1 agonists to treat neurological diseases. It “supports and drives gene expression linked to cellular growth, cellular repair, energy utilization.” In other words, it doesn’t make cells take up sugar. Instead, it has another important task—helping to keep brain cells fully functional.

This means if the brain becomes resistant to insulin—as it does with diabetes—the results can be catastrophic. “Synapses [the connections between brain cells] burn through tons of glucose,” Hölscher explains, “so if anything compromises that, then you will see the effects quite clearly.” Neurons will stop maintaining their synapses. “Synapses stop working, and eventually they disappear, and then you’re well on your way to Alzheimer or Parkinson’s,” Hölscher says.

A brain losing connections is a brain in distress, and inflammation abounds. “There’s inflammation in the brain with virtually every acute or long-term neurodegenerative disorder,” says Greig. Inflammation and insulin resistance in the brain are all linked to Alzheimer’s disease, Parkinson’s, and dementia.

It’s a connection that clinical neuroscientist Michal Schnaider Beeri has seen firsthand. The director of the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at Rutgers University in New Jersey has been following a large cohort of Israeli men for decades, looking at risk factors for issues like heart disease. As the years go by, she has seen something else: Those who developed ​t​ype 2 diabetes in midlife were nearly three times more likely to develop dementia. “Diabetes, per se, is related to faster cognitive decline, mild cognitive impairment, and high dementia risk,” she says.

Perhaps due to the drastically different roles of insulin in the body and the brain, insulin resistance in one doesn’t always mean insulin resistance in the other. “There are plenty of studies now that [show] in individuals with Alzheimer’s disease, they have insulin resistance solely in their brain,” says Elizabeth Rhea, a neuroscientist at the University of Washington in Seattle. Which means they don’t have ​​high blood sugar​, or require diabetes medicine. ​To make matters more complicated, insulin resistance in the brain isn’t detectable with a blood test—it requires brain tissue, something that’s basically impossible to get from live patients.

For diabetics, the good news is that not everyone with insulin resistance in the body has to panic about their brains. But the difficulty of detecting brain insulin resistance also means that it can wreak havoc unnoticed for years, until the effects are severe enough to become apparent. ​

By then, it’s often too late, says Natalie Rasgon, a neuroendocrinologist at the ​Icahn ​School of Medicine at Mount Sinai ​in New York City ​and director of the Center for Neuroscience in Women’s Health at Stanford University. “When you have a neurodegenerative disease, the train has left the station,” she says. “You could try to mitigate the course [of the disease], but it’s not a curable disease.”

Saving at-risk neurons

Scientists have known since the 1990s that insulin can improve the lives of cells affected by Alzheimer’s disease, fighting against the clumps of insulin-blocking, synapse-clogging beta-amyloid that build up outside of diseased cells. More insulin could help the brain fight back. A few puffs of nasal insulin, it turns out, can improve memory in people with Alzheimer’s, as well as in healthy older adults. “Even with relatively short exposure times, just a few weeks, you could shift the needle on cognition or short-term memory and some biomarkers,” Hölscher says.

The connection between improved insulin signals and cognition became visible in Schnaider Beeri’s aging men. The researcher and her colleagues began to realize that brains with Alzheimer’s looked different not only based on whether the patients had diabetes, but on whether they’d ever been treated for it. For patients who had been in treatment, their brains sometimes showed “a little less” damage than the team expected. Schnaider Beeri’s conclusion: “Maybe the drugs for diabetes are doing something to [the] pathology of Alzheimer’s.”

Other scientists and drug companies were quickly coming to the same conclusion. Surveys across more than ​one ​million patients indicated that diabetics on metformin (Glucophage) and sodium-glucose cotransporter-2 inhibitors (drugs like Jardiance) developed dementia less frequently.

(It may be possible to detect Alzheimer’s risk sooner—as early as your 20s)

Ozempic and the brain

As much as GLP-1 agonists like Ozempic and Wegovy have gained cultural relevance as weight-loss drugs, they were originally approved to treat diabetes. The GLP-1 receptor in cell membranes binds hormones released after meals, stimulating the production of insulin. Drugs that activate the GLP-1 receptor, then, also promote insulin release.

GLP-1 receptors are found in the brain, where they help brain cells grow and maintain their connections. And researchers like Greig, Li, and their colleagues have shown that the GLP-1 agonists do reduce brain injury in animal models ​​of​ stroke, traumatic brain injury, Parkinson’s, Alzheimer’s, and ALS.

Meanwhile, when it comes to humans, Rasgon and her colleagues showed in 2019 that 12 weeks of liraglutide (Victoza)—another antidiabetic medication—improved connections between the memory-critical hippocampus and other brain regions, whether the participants were insulin resistant or not. ​Even better​, a 2020 Italian study showed that liraglutide could improve memory scores in diabetes patients.

Schnaider Beeri is in the midst of a study funded by the Alzheimer’s Association—due to end in 2027—that gives diabetic patients combinations of the GLP-1 agonist semaglutide (Ozempic, Wegovy), as well as intranasal insulin in older adults who are already cognitively impaired, to find out how well the treatments might rescue their brain function.

Other scientists are pooling data from large cohorts—often from studies by pharmaceutical companies eager to find new markets for already popular drugs—to examine how many people who received GLP-1 agonists went on to develop dementia.

In an Eli Lilly-funded study known as REWIND, dulaglutide (Trulicity) reduced mild cognitive impairment rates by 12 percent. In a study funded by Novo-Nordisk, the Dutch pharmaceutical company that manufactures Ozempic, people treated with GLP-1 agonists ended up with an 11 percent decrease in risk for dementia. “I think it’s good enough to keep looking,” says Christian Torp-Pederson, the cardiologist at Nordsjællands University Hospital in Denmark ​who ​​helped lead ​the study.

Go slow, go steady, do studies

With GLP-1 agonists already helping millions of people manage diabetes and weight loss, the added bonus of lowering the risk of dementia might seem like yet another reason to start taking one. But for otherwise healthy people, the science is not as clear-cut.

First, the effect on cognition in nondiabetic brains might be too minor to matter. “The majority of patients in the GLP-1 studies, they had a prior myocardial infarction or similar,” Torp-Pedersen says. “So they were quite sick. And it is in this group we see a benefit.”

And not every study even sees the same benefits, notes Riccardo De Giorgi, a psychiatrist at the University of Oxford in England. Some show differences in inflammation, others in cognition; some studies show no changes in cognitive function at all after treatment with a GLP-1. ​​​​

“This topic has become so extremely popular, people obviously are getting quite excited,” De Giorgi says, adding, “but sometimes that means doing things a bit quickly and maybe looking for a big, sensational title—a big message in the news, rather than doing some small, incremental-step science.” He is working on a study with a single injection of semaglutide in healthy patients. “We are trying to establish whether these medications have any effects on…reward, impulsivity, emotional processing, memory and so on,” he says.

Whether a particular drug has any effect will depend on if it gets into the brain at all, Rhea notes. The brain is protected by the blood-brain barrier—a thin layer of cells that carefully filters everything passing from the bloodstream to the brain. It has transporters for some molecules and allows others through—but many need not apply.

Rhea and her colleagues have shown that while some GLP-1 agonists whoosh into the brain, others, like tirzepatide (Mounjaro, Zepbound), never cross at all. It’s possible, she says, that for cognitive benefits, existing drugs might need to be tweaked to emphasize their effect on the brain versus the body.

Of course, it would be helpful if scientists knew exactly how GLP-1 agonists were having an effect on dementia risk. Maybe insulin resistance is driving neurodegeneration, and GLP-1 agonists just make insulin signals better. “I believe when these drugs are moving in the brain, insulin resistance is reversed, which in turn enhances cognition,” Rhea says.

Others, like Greig and Li, think inflammation is the cause of cognitive decline. “The inflammatory process in the brain is a double-edged sword,” Greig says. “It’s essential to be triggered for the healing process.” Immune cells in the brain turn on in response to injury. But they need to turn off or they’ll do more harm than good. In neurodegenerative diseases, he says, the immune cells might be stuck in a pro-inflammatory state. It’s possible GLP-1 agonists might quiet these cells, keeping them from damaging the very neurons they’re meant to protect.

Schnaider Beeri thinks damage to blood vessels in the brain could play a role. Insulin receptors sit on blood vessels. Insulin resistance could be “impairing the vessel function. It could be impairing the vessel structure,” she explains. People with ​t​​ype 2 diabetes are also more susceptible to strokes and brain bleeds—which can in turn kill brain cells. As GLP-1 improves insulin signaling, the vessels could be able to function again.

The answer to how GLP-1 agonists affect the brain could, of course, be all of the above. Insulin resistance could increase inflammation, which could impair blood vessels and eventually damage cells. Blood vessels could develop insulin resistance, cause cell damage, and inflammation could be the result. GLP-1 agonists could influence all of these processes.

And while some GLP-1 drugs have been on the market for decades, scientists still aren’t sure of the long-term effects, Rhea adds. It’s far too soon to recommend that the average person start taking one as a hedge ​to ​protect their brains.

“That type of question appeared first with statins, you know, to lower cholesterol: ‘Why don’t we put statins in the drinking water?’ We could put GLP-1s in the drinking water,” Torp-Pedersen says. But we don’t put pharmaceuticals in the drinking water for good reason: “We have yet to find a drug that’s never dangerous.”

GLP-1 agonists have plenty of unpleasant side effects: Nausea and constipation are common. ​​​​And those are the ones we know about. As more and more people take Ozempic, Wegovy, Zepbound, and the like, rare side effects—like pancreatitis or even sudden blindness—will probably become increasingly apparent.

Even if it never makes sense for the average American to take GLP-1 agonists like they would take daily vitamins, the upside is considerable: An increasing body of research shows how these drugs might make a crucial impact in how we manage and mitigate the brutal effects of neurological disease. According to Alzheimer’s Disease International, more than 55 million people were living with dementia in 2020—and that number will roughly double every 20 years. Having a drug on the shelf that might lessen the effects of an increasingly prevalent enemy would be a win-win. But there’s still plenty of work to be done by ​​​​​lab scientists and clinicians alike​ before anyone can celebrate.

This article is part of Your Memory, Rewired, a National Geographic exploration into the fuzzy, fascinating frontiers of memory science—including advice on how to make your own memory more powerful. Learn more.