Alzheimer’s and Dementia

A stock photo shows an image of a brain. Researchers used AI to analyse how gut bacteria may contribute to the development of Alzheimer’s disease.© GETTY IMAGES

Comparing Dementia And Alzheimer’s Disease

When your memory slips, you might worry that it’s Alzheimer’s.

Clues to preventing Alzheimer’s come from patient who evaded disease, despite genetics. Scientists have discovered a connection between the development of Alzheimer’s disease and the bacteria in the body’s digestive system.

Using artificial intelligence, researchers at the Cleveland Clinic Genome Center in Ohio identified how metabolites produced by gut bacteria may interact with brain cell receptors, contributing to the disease. The findings could eventually lead to the development of new therapeutic interventions or drugs to prevent Alzheimer’s disease, a condition that affects nearly 7 million Americans.

Alzheimer’s disease is a progressive neurodegenerative condition that primarily affects older adults. It leads to the decline of cognitive functions such as memory, emotional regulation and reasoning. Although there is no cure, medications can slow the progression of the disease.

For the study, the team used a type of AI called machine learning to analyze more than 1.09 million potential interactions between bacterial byproducts called metabolites and cell receptors.

Bacteria release metabolites into our systems as they break down the food we eat for energy. The metabolites then interact with and influence our cells, fueling cellular processes that can be helpful or detrimental to health.

The researchers ranked metabolites and receptors by the likelihood they will interact with each other. They also examined which metabolite-receptor pairs were likely to influence Alzheimer’s disease in brain cells derived from patients with the condition.

The researchers discovered that one metabolite called agmatine may help to protect brain cells from inflammation and the subsequent damage. Specifically, they found agmatine was most likely to interact with a brain cell receptor called CA3R in Alzheimer’s disease.

When the researchers treated Alzheimer’s-affected neurons with agmatine, it directly reduced CA3R levels, which suggests that the metabolite and receptor influence each other.

Neurons treated with agmatine also had lower levels of phosphorylated tau proteins, a marker for Alzheimer’s disease.

Preventing harmful interactions between metabolites and our cells could help fight disease. However, research into this approach takes a long time because of the huge amounts of information necessary to identify a target receptor. Using AI helped to speed up the process.

“Gut metabolites are the key to many physiological processes in our bodies, and for every key there is a lock for human health and disease,” said study researcher Feixiong Cheng in a press statement.

“The problem is that we have tens of thousands of receptors and thousands of metabolites in our system, so manually figuring out which key goes into which lock has been slow and costly.”

The full findings of the study were published in Cell Reports.

Scientists at Florida State University (FSU) have discovered a potential link between gut bacteria and the likelihood of developing Alzheimer’s disease.

An estimated 6.7 million older adults have Alzheimer’s disease in the U.S., according to the Centers for Disease Control and Prevention—a figure that is expected to double by 2060.

The most common type of dementia, the disease involves memory loss and cognition issues that gradually get worse over time as the brain deteriorates.

But FSU scientists have discovered a potential reason why some people might be more likely to develop Alzheimer’s, paving the way for potential preventative treatments—and it’s all to do with the gut.

The gut is full of microorganisms, including many different strains of bacteria and yeasts. A healthier gut has a lot of these microorganisms, a wide variety of them, and a good balance between beneficial and less beneficial types.

But sometimes, guts can become out of balance. This might be because of the diet, stress, or a course of antibiotics, which can kill off gut bacteria, the good and the bad.

After a course of antibiotics, with lower all-round levels of bacteria in the gut, some strains can proliferate more than others and create imbalance—dysbiosis—in the gut.

FSU scientists found a link between Klebsiella pneumoniae, a common bacteria that has developed significant resistance to antibiotics, and the development of Alzheimer’s disease.

K. pneumoniae is notorious for causing infections in hospitalized patients, often after courses of antibiotics.

The scientists found that, after antibiotics, K. pneumoniae may overgrow in the gut, pass through the gut wall into the bloodstream, and then travel to other organs, including the brain, where it can create inflammation.

Neuroinflammation is recognized as a prominent factor that can lead to Alzheimer’s disease.

RA’s Effect on the Brain

By Linda Rath

A lot of people with rheumatoid arthritis (RA) report having trouble with memory, attention, and mental focus. They forget names and appointments, struggle to find the right words and have trouble making and carrying out plans. Some say that the loss of mental clarity, commonly called brain fog, is almost as distressing as arthritis itself.

Limited Research

It’s hard to say exactly how common fuzzy thinking is in RA because researchers have largely ignored it.

“We have relatively good literature on cognitive problems in lupus and fibromyalgia, where brain fog is well established, but nobody has really studied RA,” explains Patti Katz, PhD, a professor of medicine at the University of California, San Francisco.

Katz and her colleagues looked at 15 studies on RA and cognition published between 1994 and 2016. Many were small – less than 100 patients – and not all were high quality. Yet most showed that people with rheumatoid arthritis performed more poorly on cognitive tests than their peers or controls. Memory, verbal communication, attention, concentration and problem-solving seemed to cause the most trouble.

Who Gets It and Why?

There are several theories why cognitive problems may be more common in RA and other inflammatory types of arthritis.

Some scientists, including Mark Swain, MD, a professor at the University of Calgary in Canada, think inflammation tops the list. More than a decade ago, he and his colleagues demonstrated that chronic inflammation in the body – the result of cytokines like tumor necrosis factor (TNF) – can change the way the brain functions. The brain doesn’t change structurally, but networks of nerves start talking to each other differently. This can contribute to many disease-associated symptoms, including brain fog.

Swedish researchers reached the same conclusion after following nearly 1,500 patients with various joint disorders for two decades. They found a significantly higher rate of cognitive decline in those with RA and suggested that chronic inflammation “played an important role in increasing the risk.”

But Katz thinks it might not be that simple.

“RA is a disease that has a lot of elements, and we need to think about all of them because people are really complicated,” she says.

Some factors that may contribute to brain fog include:

• Pain. It’s well known that chronic pain can affect thinking. Some of the brain’s pain processing centers overlap with areas involved with memory and attention. When they compete for limited processing resources, pain often wins out. Pain may also rewire how the brain works.

• Depression. Depression is common in RA. Symptoms can include trouble with planning, decision-making, memory and mental clarity – the same symptoms reported by people with brain fog. Katz says one of the challenges of studying cognitive problems is the difficulty in distinguishing them from depression. Some researchers – though not Katz – see brain fog as a symptom of depression, not a separate condition.

• Cardiovascular Disease. People with RA are more likely to have narrowed or blocked arteries in the brain – the result of systemic inflammation. This can cause problems with memory, thinking and reasoning.

• Arthritis Meds. Methotrexate is a mainstay of RA treatment and corticosteroids are sometimes used for short-term pain relief. Both may cause cognitive problems, mood changes and confusion. A small study published in Toxicology and Applied Pharmacology in 2017 found that RA patients treated with methotrexate and other conventional disease-modifying antirheumatic drugs (DMARDs) had higher risk of developing dementia than those who took other medications. Moderate to high doses of corticosteroids can lead to cognitive problems in some people, more commonly women.

• Lack of Exercise. Few things have a stronger demonstrated link to brain health than exercise. Thousands of studies show the long-term benefits, but new research suggests exercise can have an immediate effect, too. Carson Smith, MD, and colleagues in the University of Maryland School of Public Health found that older adults’ memory improved significantly after a single 30-minute exercise session. A French study found that just a 15-minute jog boosted energy and mental clarity.

What the CDC Says

In 2017, Centers for Disease Control and Prevention (CDC) researchers published a study comparing cognition in more than 6,000 people with and without arthritis. Unlike earlier, smaller studies, it found no difference in brain function between the two groups. The researchers say they had different results because they considered pain, depression, lack of exercise, age and other factors linked to both brain fog and RA. Once these were accounted for, people with RA showed no more cognitive problems than other older adults. What was associated with elements of impaired brain function were a sedentary lifestyle, depression and having a lower socioeconomic level. The implication is that RA itself doesn’t cause brain fog, but factors associated with it may.

Targeting Several Risk Factors

If cognitive problems are complex, then the solution needs to be complex, too. That’s the thinking behind a groundbreaking clinical trial in Finland called the FINGER study. In this two-year randomized controlled trial involving more than 1,200 older adults with an elevated risk of dementia, lifestyle changes including an anti-inflammatory diet, exercise and brain training cut cognitive decline by 30%. Targeting several risk factors will deliver the optimal benefits.

Here are some tips that can help you keep your brain sharp:

• Sleep well. Deep, restorative sleep helps to clear away the cobwebs. Develop a healthy sleep routine and stick to it. Make sure your bedroom is cool and dark, avoid late-day caffeine and turn off screens at least an hour before bed.

• Talk to your doctor about medications. If you take conventional DMARDs or long-term corticosteroids, discuss the pros and cons of switching to another drug. Talk about your other meds, too. Some, including anticholinergics (used to treat overactive bladder, COPD and other conditions) can also cause brain fog.

• Don’t skip workouts. There’s almost nothing exercise doesn’t help. Pain, mobility, mood, fatigue and mental clarity all may improve in a single session, but the greatest benefits happen over time.

• Notice brain fog patterns. Your symptoms may be worse in the morning or when you’re tired or stressed. Try to schedule tasks that require focus and attention when you’re at your best.

• Be present. It’s easy to worry about the future, especially when you have a chronic illness. But concern about things that haven’t happened yet take up valuable mental space. Instead, focus on the present moment, says Ashira Blazer, MD, a rheumatologist and assistant professor at NYU Langone Health in New York

Bottomline, whether having RA directly contributes to cognitive impairment or not, following a healthy lifestyle and keeping your disease under control can help keep brain fog at bay.

Learn about the possible links between rheumatoid arthritis and cognitive effects and how to manage them.

INTERESTING READING: when arthritis flares up memory is low – Search

when arthritis flares up memory is low reddit – Search

An old woman looks out of a window leaning on a walking stick, with a rendering of microorganisms in the gut overlayed. Scientists have found a possible link between the bacteria in our guts, and the risk of developing Alzheimer's disease in old age. fizkes/Getty Images / Canva

Everything you need to know about Alzheimer’s disease

“Hospital-acquired and septic infections are one of the risk factors that may increase the predispositions to future neuroinflammatory and neurocognitive impairments, especially in older adults,” said last author Ravinder Nagpal, assistant professor at FSU and director of FSU’s Gut Biome Lab, in a statement.

“Hospitalizations and ICU [intensive care unit] stays, combined with antibiotic exposure, may lead to a further decline in microbiome diversity that leaves older adults at high risk not only for digestive issues but also for extra-intestinal pathologies such as neurodegenerative disorders through a dysregulation of the gut-brain axis.”

The Florida scientists discovered this by experimenting on mice, testing the microbes in their gut, blood and brain, and then testing their brain and memory function.

Mice who were given antibiotics were likely to develop gut dysbiosis, they found, and then fed the mice K. pneumoniae broth and found it took hold more easily in the imbalanced guts.

Those mice who developed infections were then found to have severe abscesses on and around the brain, brain inflammation, and worse cognitive and memory function.

The scientists concluded that disruptions to the gut could lead to problems with the brain, including the development of neurodegenerative diseases such as Alzheimer’s.

This study was published in the scientific journal The Journal of Infectious Diseases in September.

It was funded by the Infectious Disease Society of America and the Florida Department of Health.

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Reference

Park, G., Kadyan, S., Hochuli, N., Salazar, G., Laitano, O., Chakrabarty, P., Efron, P. A., Zafar, M. A., Wilber, A., Nagpal, R. (2024). An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice, The Journal of Infectious Diseases 230(2). http://dx.doi.org/10.1093/infdis/jiae165

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