Weight loss is usually considered a good thing, unexpected and extreme weight loss can be a sign of something in your body going very wrong. There could be some underlying issues that are causing your body to pull weight and nutrition from your muscles and body fat to keep you going. As you grow old, your limbs grow weaker, and same for your muscles, so you do lose some weight as you age, but losing a lot of it too quickly could be a sign of something much worse, Dementia. A recent study published in JAMA Network Open 2025 Cardiometabolic Trajectories Preceding Dementia in Community-Dwelling Older Individuals, has identified potential early indicators of dementia, including significant weight loss and specific digestive changes, appearing years before noticeable cognitive decline.

The study showed that people who later got dementia had their Body Mass Index, or BMI, go down faster than those who stayed healthy. BMI is a way to see if someone's weight is healthy for their height. This drop in BMI started happening many years before they were told they had dementia, sometimes as early as 11 years ago. Also, these people often started with a lower BMI to begin with. So, even though everyone's weight might change a little as they get older, the people who developed dementia had a much bigger and faster weight loss.

What Are Some Other Indicators Of Dementia?

Along with their BMI, the size of their waist also changed. People who ended up with dementia had smaller waist sizes, and this difference was noticeable about 10 years before they were diagnosed. This means that their bodies were changing in ways that showed up long before they or their doctors noticed any problems. So, not only was there weight loss, but also a loss of abdominal fat. This measurement is important because fat around the waist can be related to other health issues.

The study also found changes in their blood. Specifically, the "good" cholesterol, called HDL, went up in people who developed dementia. This increase happened about five years before they were diagnosed. It's tricky because HDL is usually seen as a good thing for your heart. But in this case, it seems like it might be a sign of changes happening in the brain. Scientists are still trying to understand why this happens.

Weight Loss Doesn’t Cause Dementia, Dementia Causes Weight Loss

When we see that people with dementia lose weight, it's easy to think that the weight loss is what caused dementia. But experts think it's the other way around. They call this "reverse causation." This means that the brain changes that cause dementia also cause people to lose weight. The brain changes can affect things like appetite, how the body uses food, and how people go about their daily lives. For example, people might forget to eat, have trouble making meals, or move around less.

While the study revealed a lot about different indicators of dementia and bodily changes, there are many limitations to the study. Everyone loses some weight as they get older. So, it's hard to know when weight loss is just a normal part of aging and when it's a sign of dementia. The study found that people with dementia lost weight faster, but it's still tricky to tell the difference in everyday life. Doctors need to look at other things, like memory tests, to figure out if someone's weight loss is a cause for concern.

If someone is losing weight without trying, and they're also having problems with their memory or thinking, it's important to talk to a doctor. It's not just about the weight loss; it's about the whole picture.

Obesity during the 20s and 30s can fuel the risk of many lifestyle disorders like type 2 diabetes, cardiovascular diseases, metabolic syndrome, non-alcoholic fatty liver disease, sleep apnea and many others.

But according to a large study published in Annals of Internal Medicine, obesity could also increase the risk of developing cancer before midlife. The study identified higher chances of thyroid, endometrial and ovarian cancers.

How Was The Study Conducted?

Researchers examined health records of 6,313,338 adults in South Korea, aged between 20 to 39 years, who had no previous history of cancer.

Participants were followed for an average of 11.2 years to study the relationship between body weight and cancer risk.

During the follow-up period, 151,893 cancer cases were recorded. The findings showed that cancer risk increased in people with higher body mass index (BMI).

The researchers found that the 10-year total incidence of cancer was 1.84% among people with normal body weight. This increased to 2.24% among those with class I obesity and 2.62% among those with class II obesity.

In other words, the 10-year cancer incidence was approximately 0.78 percentage points higher among people with class II obesity than among those with normal weight.

The researchers also found that people with abdominal obesity were at higher cancer risk than those who didn’t have.

Among people with class I obesity, the 10-year cancer incidence was 2.45% in those with abdominal obesity, compared with 2.13% in those without it.

“Because abdominal obesity may be an important indicator for distinguishing cancer risk, it is important to manage waist circumference along with weight from a young age,” the authors wrote.

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Three Cancers Linked To Early Adulthood Obesity

The study identified particularly strong associations between obesity and cancers involving the thyroid and female reproductive system.

Thyroid cancer: Excess body weight has previously been linked with changes in metabolic and hormonal changes that may affect thyroid cancer development.

Endometrial cancer: Obesity can increase oestrogen levels because fat tissue produces this hormone. Prolonged exposure to excess oestrogen can stimulate the growth of the uterine lining and increase the risk of endometrial cancer.

Ovarian cancer: The relationship between obesity and ovarian cancer is complex and may involve inflammation, insulin resistance and hormonal changes.

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Obesity & Cancer Risk

Obesity causes several biological changes that may contribute to cancer development. One of them is chronic inflammation.

Excess fat tissue can fuel inflammation that may create an favourable environment for abnormal cell growth.

Obesity can also lead to insulin resistance, in which the body’s cells respond less effectively to insulin. This can cause higher insulin levels, which may fuel cell growth and proliferation.

Hormonal changes are also a factor. Fat tissue produces oestrogen, and higher levels of this hormone have been linked with cancers like endometrial and ovarian.

The study authors wrote, "Some cancers have recently become more common even among younger people, and this study confirmed that obesity in young adults is significantly associated with the development of these cancers."

Scientists have discovered a previously unknown mechanism that could explain why high cholesterol diet makes it challenging for the liver to remove bad cholesterol from the bloodstream. Researchers have also identified an experimental drug that blocks this process, offering a new method for treating high cholesterol.

The findings are published in the journal Nature by researchers from the University of California San Diego School of Medicine. Their experiments showed that blocking a specific enzyme called cathepsin A (CTSA) helped retain the liver's ability to clear low-density lipoprotein (LDL), commonly known as bad cholesterol.

In mice, inhibiting this enzyme stabilised LDL receptors in liver cells, reducing LDL cholesterol.

"We've known for a long time that a high-cholesterol diet reduces the liver's ability to clear cholesterol from the blood, but we didn't fully understand why," said senior author Alan Saltiel, professor of medicine at UC San Diego School of Medicine. "This new discovery explains a critical piece of that puzzle."

More About The Experiment

The liver plays a key role in regulating cholesterol levels. It uses LDL receptors located on the surface of liver cells to capture LDL cholesterol from the bloodstream.

When fewer of these receptors are available, the liver becomes less efficient at removing LDL cholesterol, allowing it to increase in the bloodstream. The researchers discovered that consuming high amounts of dietary cholesterol activates a protein called Ral. This increases the activity of CTSA, an enzyme that breaks down LDL receptors.

As these receptors are lost, the liver's ability to clear bad cholesterol declines. When researchers blocked CTSA using a small molecule inhibitor, LDL receptors became more stable and LDL cholesterol levels decreased dramatically in mice.

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Experimental Drug That Can Help Lower Cholesterol

The discovery has sparked interest as researchers have identified an experimental drug that targets CTSA. The drug was originally developed as a possible treatment option for heart failure. Although its development for that purpose was discontinued for other reasons, it had already completed a Phase 1 clinical trial, which evaluated its safety in humans.

This previous test could help researchers move towards studying its ability as a cholesterol treatment. However, the drug has not yet been shown to lower LDL cholesterol in humans.

"There's still a real need for new cholesterol-lowering options, since some people can't get to safe levels even with the drugs we have now," Saltiel said.

He added, "This new pathway we discovered is completely separate from anything that existing drugs target, so it gives us a new opportunity to fill that gap."

The researchers hope to test the experimental CTSA inhibitor in a Phase 2 clinical trial to determine whether it can safely and effectively lower cholesterol in people. If successful, the approach could offer another option for people who struggle to control LDL cholesterol despite using existing treatments.

Saltiel said, "Luckily, there's an experimental drug sitting on the shelf that's already been shown to be safe in humans."

"We hope to test whether this might be effective by conducting a clinical trial -- which could potentially bring a new treatment option to patients much sooner than would have been expected."

Irritable bowel syndrome (IBS) is often characterised by digestive symptoms like abdominal pain, bloating, constipation and diarrhoea. However, the condition involves more than the digestive system.

A new review published in The Lancet explains how interactions between the gut and brain, changes in the gut microbiome, immune activity and the body's response to pain can contribute to the development of symptoms.

The review, titled Irritable bowel syndrome and related disorders of gut-brain interaction, brings focuses on biological and psychological evidence behind IBS. Researchers describe it as a disorder of gut-brain interaction, in which signals between the digestive system and the central nervous system affect gut function.

The authors also discuss chronic constipation and functional diarrhoea, which belong to the bigger group of disorders related to gut-brain interaction. These conditions may affect an estimated 20% of the global population.

What Is The Gut-Brain Connection In IBS?

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The gut and brain communicate continuously through a complex network that involves the central nervous system, autonomic nervous system, enteric nervous system and hypothalamic-pituitary-adrenal (HPA) axis.

The brain can influence intestinal movement, secretion and sensitivity, while signals from the gut can affect how the brain processes pain and other sensations.

In people with IBS, this communication may become disrupted. The result can be changes in bowel movements, more sensitivity to normal digestive processes and abdominal discomfort.

The authors said, “These central and peripheral mechanisms can act in an integrated way to cause IBS symptoms, via the gut-brain axis.”

For instance, a person with IBS may experience pain or bloating even when the amount of gas or intestinal movement would not cause discomfort in someone without the condition. This is due to a condition called visceral hypersensitivity, in which the nerves supplying the digestive organs become unusually sensitive to internal sensations.

The review explains that changes in both peripheral mechanisms within the gut and central mechanisms involving the brain can contribute to symptoms.

Gut Bacteria And Inflammation May Contribute To IBS

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The gut microbiome, which consists of microorganisms living in the digestive tract, is another important part of the gut-brain connection.

Changes in the composition and activity of gut bacteria may impact intestinal function, immune responses and communication with the nervous system. The review identifies the following:

• Gut infections: Gastrointestinal infections can trigger IBS symptoms in some people, even after the initial infection has subsided.
• Altered gut microbiome: Changes in intestinal bacteria may affect digestion, immune activity and gut function.
• Increased intestinal permeability: Changes in the intestinal barrier may allow substances to pass through more easily, potentially contributing to immune activation.
• Low-grade inflammation: Mild inflammation in the intestinal lining and changes in immune function may contribute to symptoms.
• Abnormal gut movement: Changes in gastrointestinal motility can cause food and waste to move through the digestive tract too quickly or too slowly.
• Visceral hypersensitivity: Increased sensitivity in the gut can make normal digestive processes feel painful.

Mental Health And IBS

Psychological health is another component of the gut-brain axis. Stress, anxiety and other psychological difficulties can influence how the brain processes pain and communicates with the digestive system.

The HPA axis, which helps regulate the body's response to stress, plays a role in this process . Changes in stress levels can affect gut movement, secretion and sensitivity.

Currently, there is no single biomarker that can diagnose IBS. Doctors assess symptoms, medical history and clinical findings, while using tests to rule out other conditions.

The review highlights that some underlying mechanisms can already be measured through approved tests and questionnaires. These include abnormal bile acid metabolism, accelerated movement of contents through the colon and psychological conditions.