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  #1   ^
Old Tue, Jul-30-24, 09:52
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Calianna Calianna is offline
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Default Ozempic-like weight loss drugs may protect against Alzheimer's

Practically every news service has picked up this story (CNN, CNBC, USA Today Forbes, Business Insider and so on...), but this one on NBC is the one that the very title practically calls it a miracle drug to prevent alzheimer's.

Quote:
Ozempic-like weight loss drugs may protect against Alzheimer's

A drug similar to Ozempic, called liraglutide, slowed cognitive decline in people with mild Alzheimer's disease. A weight loss drug similar to Ozempic appeared to slow cognitive decline in patients with mild Alzheimer’s disease, new research presented Tuesday at the Alzheimer’s Association International Conference in Philadelphia finds.

The findings, which have not yet been published in a peer-reviewed journal, add to the growing evidence that GLP-1 agonists — a class of medications that includes the popular diabetes and weight loss drugs Ozempic and Wegovy, from Novo Nordisk, and Mounjaro and Zepbound, from Eli Lilly — may also protect the brain.

“What we’ve shown is that these GLP-1s have great potential to be a treatment for Alzheimer’s disease,” said Dr. Paul Edison, a professor of neuroscience at Imperial College London who presented the findings Tuesday. “As a class of drugs, this holds great promise.”

Early evidence has hinted at GLP-1 drugs’ brain-boosting potential. Semaglutide, the active ingredient in Ozempic and Wegovy, has been shown in studies to cut the risk of dementia in patients with Type 2 diabetes. Type 2 diabetes is a known risk factor for the disease.

Novo Nordisk is running two phase 3 clinical trials that will compare semaglutide to a placebo in more than 3,000 patients with mild cognitive impairment or early-stage Alzheimer’s disease. The trial results are expected to be released sometime in 2025. In a statement, a Novo Nordisk spokesperson said there is “an urgent need for treatments that can slow the progression of Alzheimer’s disease.”

The new research presented by Edison looked at liraglutide, the active ingredient used in two of Novo Nordisk’s older GLP-1 drugs, Saxenda, a weight loss drug, and Victoza, a diabetes drug. The midstage clinical trial included about 200 people in the United Kingdom who got daily injections of either liraglutide or a placebo.

After one year, cognitive decline in the patients who got liraglutide had slowed by as much as 18% compared to those who didn’t get the drug, based on the Alzheimer’s Disease Assessment Scale, which tracks the progression of the disease by assessing memory, language, skills, understanding and reasoning abilities.

The drug was also shown to reduce shrinkage in parts of the brain responsible for memory, learning and decision-making by nearly 50%. Shrinkage of the brain, also known as brain atrophy, is often associated with the severity of cognitive decline in people with dementia and Alzheimer’s.

“I think there’s some hope for these drugs,” said Dr. Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minnesota, who is not involved with the research. “Their primary use is diabetes and weight loss, but you’ve probably also seen that they may be useful for sleep apnea and heart disease. So all of these effects cumulatively may be very beneficial to the brain.”

The next wave of Alzheimer’s treatments

Nearly 7 million people in the U.S. have Alzheimer’s disease, according to the Alzheimer’s Association. By 2050, the number is projected to almost double to 13 million.

The disease has no known cure.

Within the past two years, the Food and Drug Administration has approved two drugs — Biogen’s Leqembi and Lilly’s Kisunla — that marginally slow the progression of Alzheimer’s by targeting the disease’s hallmark amyloid plaques in the brain. They’re the only drugs on the market available to treat the disease, but they’re pricey and can come with serious side effects, including brain swelling and brain bleeding.

Dr. Maria Carrillo, the chief science officer at the Alzheimer’s Association, said she expects that GLP-1 drugs may be the next advancement in the treatment of the disease, most likely used in combination with the amyloid-fighting drugs.

“I think the first thing out of the gate will be the GLP-1s,” Carrillo said.

If late-stage trials go well, FDA approval could happen as early as next year, she said. But combination treatment of amyloid drugs and GLP-1s is most likely already happening in the real world, Carrillo added, noting that many people with Alzheimer’s disease also have diabetes or obesity and may already be taking a GLP-1 medication.

“Those combinations are already happening,” she said. “They’re just not FDA-approved combinations.”

How might GLP-1s protect the brain?

Dr. Alberto Espay, a neurologist at the University of Cincinnati College of Medicine, said the key questions that remain are how do GLP-1s help protect the brain and by how much.

The fact that they appear to help makes sense: Alzheimer’s, he said, is thought to be a “syndrome of many diseases caused by different biological, toxic or infectious exposures.”

Petersen, of the Mayo Clinic, agreed. “I think the data are accumulating across the board for a variety of different disorders and mechanisms,” he said. “Any one of these factors, diabetes, obesity, all of these can have deleterious effects on cognitive functions. If you treat those underlying conditions, you make it a beneficial positive effect of cognitive function.”

The existing Alzheimer’s drugs, Leqembi and Kisunla, target only one component of the disease: amyloid plaque in the brain.

The GLP-1 drugs, Petersen said, could work in “nonspecific” ways.

“I don’t think that this class of drugs necessarily will have specific actions on Alzheimer’s disease if you define Alzheimer’s disease by the presence of plaques and tangles of amyloid and tau,” he said. “On the other hand, if these drugs have anti-inflammatory kinds of actions or other cerebrovascular actions, that could be very important.”

Edison said that the liraglutide study found that people who got the drug had reductions in inflammation, insulin resistance and the formation of tau, a protein in the brain that is thought to contribute to Alzheimer’s. They also had improvements in overall brain function.

“If you want to have very effective treatment, what you need is not only targeting amyloid. You have to target other pathological forces, as well,” he said.

Espay said of the liraglutide results: “This looks promising. If this is replicated in a phase 3 trial, it could become the first truly disease-modifying treatment in Alzheimer’s disease.”


https://www.nbcnews.com/health/heal...mers-rcna163459
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  #2   ^
Old Tue, Jul-30-24, 10:26
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Calianna Calianna is offline
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We've talked repeatedly about how the health problems that weight loss corrects just happen to be the same ones that semaglutide drugs correct.

Well this one actually tells me that it's not even a matter of correcting the problem with weight loss since these drugs apparently slow the progression of Alzhemier's too. Very often those who are not seriously overweight (much less morbidly obese) get alzhemiers. And then alzheimer's patients end up losing a lot of weight as the disease progresses.

There's long been speculation that it's blood sugar issues (at least in part) that causes alzheimers.

My mother had alzheimer's and she was definitely a sugar-holic. She always had normal blood sugars though - if it's related sugar/carb consumption and blood sugars, surely it also has to do with insulin levels.

Mom never gorged on sweets - her eating was always very controlled, but she always hated the taste and texture of "grease" so she ate very, very little fat. By the early 1990's she was thoroughly convinced by the Powers That Be that she needed to eat as little fat as possible, and stick to very small servings of protein. (It should be noted that she rarely ate any dairy products - lifelong stomach upset from dairy products, so she was missing protein from dairy sources too, while drinking juices, which provided even more sugar)

When her energy would get low during the day, she'd say she needed some sugar. Sometimes that meant a piece of hard candy or a piece of chocolate, but it was just as likely she'd have a handful of grapes or a piece of fruit. She always had a cake in the house (for many years she was making what she called "breakfast cake", which had oats along with the white flour, and lot of dried fruit mixed in with lots of sugar - sort of a cross between zucchini bread or banana bread and fruit cake)

She almost always ate bread with meals - approx 30-50 carbs worth of bread at every meal, often with a thin smear of jelly on a roll. As her alzheimers advanced, she ate more and more carbs - her caregivers said she started globbing about an inch of jelly on her roll at mealtime, which would have been easily 10 times as much as she used when I was a kid.


My point in all this is that it's not the overweight that's the problem in all these diseases that the semaglutide type drugs are "fixing" - the weight is only a symptom.

The real problem is the high carb diet that THEY want every man, woman, and child to eat.

Cut the carbs and you lose significant amounts of weight, get your blood sugar on a much more even keel, and correct a plethora of health conditions.
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Old Tue, Jul-30-24, 10:43
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WereBear WereBear is online now
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I'm sorry to hear about your mother. The increase in sugar intake is an attempt for the brain to get fuel.

This broken pathway is what ketones bypass. But to get them a good diet is essential. By the time people refuse to eat hearty meals I don't know what can be done.

What a GLP-1 medication is doing is not specific to Alzheimer's. The threat is more than glycation, because the physical crushing of organs, nerves, and pathways cause damage, too.
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Old Tue, Jul-30-24, 11:40
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Calianna Calianna is offline
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Originally Posted by WereBear
I'm sorry to hear about your mother. The increase in sugar intake is an attempt for the brain to get fuel.

This broken pathway is what ketones bypass. But to get them a good diet is essential. By the time people refuse to eat hearty meals I don't know what can be done.

What a GLP-1 medication is doing is not specific to Alzheimer's. The threat is more than glycation, because the physical crushing of organs, nerves, and pathways cause damage, too.


Mom was just a couple months shy of 94 when she died, and I think you need to expect some mental deterioration at that age in most cases, but in my opinion the mental deterioration had been going on for at least 15 years.

My brother says 11 years, but he saw her every day, which I think made it more difficult to recognize the small changes that started occurring years earlier. I live much further away and often didn't see her for several months at a time, so it was a lot more difficult for me to "explain away" the changes that I saw from one visit to the next.

It wasn't that she was refusing to heat a good diet - it was the definition she'd been convinced constituted a healthy diet, which as her mental ability started to go, she did as you said and wanted more and more sugar (and starch - since that converts to glucose even faster than sugar) just to keep herself going throughout the day. I can certainly identify with that from my decades on a low fat, minimal protein, "heart healthy diet" - I was utterly exhausted all the time, while constantly giving in to cravings for sweets and starches.
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Old Sat, Aug-03-24, 00:39
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Demi Demi is offline
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Quote:
Ozempic seems like a miracle drug. But what’s it doing to our brains?

The weight-loss jabs have apparently helped people kick habits from smoking to shopping, although scientists remain wary about recommending it as an addiction treatment


It began with anecdotes. There were the people taking Ozempic for type 2 diabetes who found that they no longer craved the cigarettes that had caused that diabetes. There were those using the drug to treat their weight loss who reported that as well as wanting smaller portions of food at dinner, they were also satisfied with a smaller glass of wine alongside.

Nail biters, according to some accounts, stopped biting. Compulsive shoppers felt less compulsion. One man complained to his doctor that when he went fishing he no longer felt the need to drink 18 lagers. He was, he lamented, “No fun at the beach.”

It seemed like Ozempic was not just changing their bodies. In some sense it was changing their minds.

Then came the studies. In laboratories rats were given various addictions — the full range of human vices — then given the new class of weight-loss drugs. They stopped being junkies — or, at the very least, were less dedicated rodent junkies. In humans, data is starting to come through too. Just this week, a study found that those with diabetes taking Ozempic were significantly less likely to seek treatment for tobacco-use disorder.

The trials we have are at an early stage, mainly observational, and some are ambiguous. But taken together, tentatively, they point in the same direction.

“We are seeing really positive findings,” said Sue Grigson, from Penn State University, who has conducted research showing that the new class of weight-loss drugs appear to help in opioid addiction. “The community who studies addiction is really, really enthusiastic and hopeful because we haven’t had a new drug for a couple of decades.” And those drugs they do have often aren’t that good.

It has been quite a journey. Ozempic began as a powerful drug for diabetes. After giving it to thousands of people and following their progress it was discovered that it was also a powerful drug for weight loss. There is good evidence that, independent of weight loss, it could prevent heart attacks — and maybe Alzheimer’s.

Now, researchers think it might well do something else that could be equally powerful: it may be an all-purpose treatment for addiction. There is a lot of excitement; there is also caution. Assuming it really is tackling addiction, how is it doing it? And if it can alter our desires for things that are bad, why would it not also alter them for things that are good?

“That’s a very critical question,” said Grigson. “And I don’t think the answer is really known yet … What does it do to other motivations, like wanting to go on a run? Or wanting to, you know, work like a dog to meet a certain deadline or goal? We need to know what this medicine is doing to our behaviour and our thinking, and our mood.”

It needn’t be bad news. It could well be that, rather than deadening the good with the bad it does the reverse. When people lose weight, they gain motivation. When they aren’t craving food or cigarettes, they gain focus. Through demotivating us for some things, these drugs could motivate us for others.

That’s one scenario. But it’s only a scenario. Given that, by some estimates, a fifth of the population could soon be taking these drugs, Grigson thinks it is time to find out. “We really need real data.”

Ozempic is merely the best known of a new class of drugs known as GLP-1 agonists. They trace their origin to the 1990s, when researchers realised they mimicked a gut hormone that promotes insulin production. If you took them, you controlled type 2 diabetes. You also, they found, promoted satiety.

But GLP-1 receptors do not only live in the gut. And so, it has been found, the drugs do not only have an effect in the gut. “They seem to be dampening down the reward circuitry in the brain — the motivation to seek rewarding things, whether that’s food or also drugs,” said Tony Goldstone, associate professor in the department of brain sciences at Imperial College London.

What does this mean? The brain doesn’t have an “addiction to bad things” circuit. “Remember that the drugs we abuse have hijacked our reward systems. We have reward systems that were developed to help us get food, water, salt and sex. Those are the evolutionary drives,” said Goldstone.

We know that Ozempic makes us want food less. We actually also know — although it’s not the reason why its maker Novo Nordisk is worth more than the GDP of Denmark — that it makes us drink less water. On salt and sex, said Goldstone, “there’s no data”. And of course, even if there is a pharmacological effect it could well be more than counterbalanced, again, by physical ones — such as the libido boost through being thinner.

The concern, of course, is that Ozempic and similar drugs could create a world that is thin, abstemious, but joyless. “People have been worried that maybe people are not enjoying anything. Maybe they are getting depressed.” There’s a word for it: anhedonia.

The highly convincing riposte to that concern is, simply, we have good data to show it doesn’t. People have been taking these drugs for years, in their tens of thousands — and we just don’t see it. They are not quitting because they have lost their joie de vivre.

Interestingly, for those teasing out what is going on neurologically, people on Ozempic usually still enjoy food, they just enjoy less of it. This drug could be giving us insights into our minds. “Pleasure and motivation may be slightly separate,” said Goldstone. “There might be different circuits.”

So for now, as he and his colleagues wait for better data, for the trials that will show if it works, where it works — and how to use it for addiction — there is cautious hope. It won’t be a “wonder drug”, said Grigson. But she is increasingly sure that, for addiction, it may be a very good one.

Goldstone is also hopeful, albeit cautiously so. “As always happens whenever there’s a new drug, there’s lots of enthusiasm. You swing one way then another, and end up somewhere in the middle.” One key concern of his is that addicts — especially alcoholics — are often already malnourished. It may not be a good idea to give them a slimming drug. Even so, he said, “There do seem to be a lot of potential benefits with not a huge amount of downsides as yet.”

And yet, said Grigson, in the next few years we do need to keep an eye on those downsides. “Drive and motivation are important.” If, unwittingly, we give a large fraction of the population a drug that chips away at their grit, even a little bit, then that’s a consideration. “Think about the mountains that people have to climb to solve certain problems. We need them to climb those mountains. And you certainly don’t want to slow them down.”

https://www.thetimes.com/uk/healthc...rains-fqkwgn5q5
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Old Sat, Aug-03-24, 02:55
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WereBear WereBear is online now
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Quote:
The weight-loss jabs have apparently helped people kick habits from smoking to shopping, although scientists remain wary about recommending it as an addiction treatment


Obviously targeting some kind of "learning center" and perhaps if they studied why carbs create addiction we'd all know more.

I can tell you that alcoholism has been studied as a B vitamin deficiency (they are all vital, but B12 the most) with some success, likewise it is connected to what might be called "sugar reward" in the brain. This is all stuff which fits in with people suffering from malnutrition, and responding by cramming in more high carb/low nutrient food, which wreaks havoc and makes things worse.

Another thing that fits into the malnutrition angle is how so many people on Carnivore (two main reasons, difficulty with weight loss and/or autoimmune issues) and they are reporting that their alcohol, tobacco, even compulsive thoughts, diminish and fade away.

Also, my therapeutic niacin regimen, while I researched it, turned up a few stories of people who found that niacin did similar work for them. Likewise, I find the mental stability from the lack of anxiety keeping me on my regimen, for years now.

And believe me when I say there's a been a few anxious years lately, for everyone so the fact I'm actually getting better now is also about my niacin.

All of these mental notes are much more worth following up. But our drug research now isn't about helping people. It's about something a company can patent and sell. That's all they are looking for.

That's why it's a big mystery. No one is chasing easy & cheap & tapping into the body's real power. When that's what we need.
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Old Sat, Aug-03-24, 08:58
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Calianna Calianna is offline
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Looking at it from the addiction angle, it's interesting that it seems to inhibit behaviors related to addictive substances: alcohol, drugs, shopping, food.

We know that carbs in general can be extremely addictive - it's one reason why there are (just as a rough guess based on how many pages of user names there are under each letter of the alphabet) thousands of members on this site, but very few are currently active members: It's incredibly difficult to give up carbs in a world where practically everything in the grocery stores and on restaurant menus is carb-based, especially as those carbs are tweaked, and more highly processed to make them more and more addictive.



One thing I've noticed is that because the drug makes it difficult to digest foods that are more satiating (proteins and fats), most users are still eating mostly carbs. The ones on those drugs who are avoiding most carbs are doing it for reasons other than weight loss (because they can eat anything they want on the drugs, and don't feel the need to eat a LC diet to promote weight loss). But when they bring their diet down to mostly protein, they seem to be having a very difficult time eating more than a very small portion of mostly protein, especially if the protein comes with a decent amount of fat. They're already not hungry most of the time because of the drugs and can really only eat a fairly limited amount of carbs, but doing it significantly lower in carbs results in very low calorie consumption.

But then while off the drugs (or as the weekly shot wears off), they lose all control and want to eat everything in sight... including carbs. In fact carbs seem to be what they crave the most as the shot wears off, so they're desperate for their next "fix". The real question is are they more desperate for the next shot to calm the carb and food in general cravings, or more desperate for the amount of carby food they used to eat?

Is this how it works for other addictions too? Will the alcoholic make up for a week of no alcohol by going on a huge bender when the shot wears off? Will the shopaholic put dozens of things they want but don't need in their Amazon cart and hit "checkout" the day their shot wears off?

In the end, is it better to have 6 days of drug induced control... and one day of unbridled addictive behavior? OR find some other, more reliable way of stemming the addiction for good? Because the drugs are not really helping them kick the carb addiction, just suppressing it temporarily.
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