Time Until Dementia Symptoms Appear Can be Estimated Via Brain Scan

Tamara Bhandari wrote . . . . . . . . .

Researchers at Washington University School of Medicine in St. Louis have developed an approach to estimating when a person with no cognitive symptoms will start showing signs of Alzheimer’s dementia based on data from brain scans and the person’s age.

Researchers at Washington University School of Medicine in St. Louis have developed an approach to estimating when a person who is likely to develop Alzheimer’s disease, but has no cognitive symptoms, will start showing signs of Alzheimer’s dementia.

The algorithm, available online in the journal Neurology, uses data from a kind of brain scan known as amyloid positron emission tomography (PET) to gauge brain levels of the key Alzheimer’s protein amyloid beta.

In those who eventually develop Alzheimer’s dementia, amyloid silently builds up in the brain for up to two decades before the first signs of confusion and forgetfulness appear. Amyloid PET scans already are used widely in Alzheimer’s research, and this algorithm represents a new way of analyzing such scans to approximate when symptoms will arise. Using a person’s age and data from a single amyloid PET scan, the algorithm yields an estimate of how far a person has progressed toward dementia — and how much time is left before cognitive impairment sets in.

“I perform amyloid PET scans for research studies, and when I tell cognitively normal individuals about positive results, the first question is always, ‘How long do I have until I get dementia?’,” said senior author Suzanne Schindler, MD, PhD, an assistant professor of neurology. “Until now, the answer I’d have to give was something like, ‘You have an increased risk of developing dementia in the next five years.’ But what does that mean? Individuals want to know when they are likely to develop symptoms, not just whether they are at higher risk.”

Schindler and colleagues analyzed amyloid PET scans from 236 people participating in Alzheimer’s research studies through Washington University’s Charles F. and Joanne Knight Alzheimer Disease Research Center. The participants were an average of 67 years old at the beginning of the study. All participants underwent at least two brain scans an average of 4½ years apart. The researchers applied a widely used metric known as the standard uptake value ratio (SUVR) to the scans to estimate the amount of amyloid in each participant’s brain at each time point.

The researchers also accessed over 1,300 clinical assessments on 180 of the participants. The assessments typically were performed every one to three years. Most participants were cognitively normal at the start of data collection, so the repeated assessments allowed the researchers to pinpoint when each participant’s cognitive skills began to slip.

Schindler spent years trying to figure out how to use the data in amyloid PET scans to estimate the age at which symptoms would appear. The breakthrough came when she realized that amyloid accumulation has a tipping point and that each individual hits that tipping point at a different age. After this tipping point, amyloid accumulation follows a reliable trajectory.

“You may hit the tipping point when you’re 50; it may happen when you’re 80; it may never happen,” Schindler said. “But once you pass the tipping point, you’re going to accumulate high levels of amyloid that are likely to cause dementia. If we know how much amyloid someone has right now, we can calculate how long ago they hit the tipping point and estimate how much longer it will be until they are likely to develop symptoms.”

People in the study who reached the tipping point at younger ages took longer to develop cognitive symptoms than those who reached it later in life. Participants who hit the tipping point at age 50 typically took nearly 20 years to develop symptoms; those who hit it at age 80 took less than 10 years.

“When we look at the brains of relatively young people who have died with Alzheimer’s, they typically look pretty healthy, other than Alzheimer’s,” Schindler said. “But older people more frequently have damage to the brain from other causes, so their cognitive reserves are lower, and it takes less amyloid to cause impairment.”

The power of this new technique is that it requires just one brain scan, plus the person’s age. With that data, the model can estimate the time to symptom onset, plus or minus several years. In this study, the correlation between the expected age of symptom onset and the true age at diagnosis was better than 0.9 on a scale of 0 (no correlation) to 1 (perfect correlation).

After age, the genetic variant APOE4 is the strongest risk factor for Alzheimer’s dementia. People who carry one copy of the variant are two to three times more likely to develop Alzheimer’s dementia than the general population, and people who carry two copies are 10 times more likely. In this study, people with the high-risk variant hit the tipping point younger, but once that point was passed, they followed the same trajectory as everyone else.

“APOE4 seems to have a seeding effect,” Schindler said. “At very low levels, below the tipping point, you see amyloid rising in people with APOE4 while it’s not changing in people without APOE4. That means APOE4 carriers are going to hit the tipping point sooner. People with two copies of APOE4 hit the tipping point about 10 years earlier than people with no copies. But after that point, we see no difference between the APOE4 carriers and noncarriers.”

With an out-of-pocket cost of around $6,000, amyloid PET brain scans may be financially out of reach for many people. However, this algorithm could help accelerate the pace of drug development by streamlining clinical trials.

“Most participants in clinical trials designed to prevent or slow Alzheimer’s symptoms do not develop symptoms during the trials,” Schindler said. “That’s a lot of time and effort — for the participants as well as the researchers — that doesn’t yield useful data. If we could do trials only on people who are likely to develop symptoms in the next few years, that would make the process of finding therapies much more efficient.”

Source: Washington University School of Medicine

Diets That Lower Brain Iron Could Keep You Sharp

Amy Norton wrote . . . . . . . . .

Older adults who regularly eat foods like fish, nuts and olive oil may have less iron accumulation in their brains, as well as sharper memories, a small study suggests.

The brain requires a certain level of iron to function normally, but the aging brain can accumulate an excess amount. And that excess iron has been linked to cognitive decline — a slow deterioration in memory and thinking skills that can lead to dementia.

It’s not yet clear that the extra iron actually causes mental decline, or that limiting its buildup will stave off dementia, said Valentinos Zachariou, the lead researcher on the new study.

But diet stands as one potential way to do that, said Zachariou, a neuroscience researcher at the University of Kentucky, in Lexington.

His team found hints that certain dietary nutrients might be protective — including vitamin E and particular fatty acids found in foods like fish, nuts and olive and safflower oils.

Using MRI brain scans, the researchers found that older adults with the highest intakes of those nutrients tended to have smaller iron concentrations in their brain tissue. They also performed better, on average, on standard memory tests, versus their peers whose diets had a relative lack of those nutrients.

The findings show only correlations, and do not prove cause and effect, Zachariou stressed.

What’s needed, he said, is an “intervention” trial that directly tests the effects of a diet high in the nutrients.

The study, published online recently in Neurobiology of Aging, is not the first to link diet habits to slower cognitive decline.

The classic Mediterranean diet — high in fish, olive oil, vegetables and whole grains — has been tied to sharper mental acuity in older adults. The same is true of an eating pattern dubbed the MIND diet, which borrows from the Mediterranean diet and also emphasizes berries and leafy green vegetables (a source of vitamin E, among other nutrients).

Zachariou said his study did not focus on any particular diet. Instead, his team was interested in certain nutrients that, based on past lab research, may help remove excess brain iron or counter its ill effects.

“But,” Zachariou noted, “there is a lot of overlap between what we found and the Mediterranean diet.”

The study involved 73 healthy adults aged 61 to 86. They reported on their intake of particular foods in the past month, as well as their exercise and drinking habits.

In the end, a group of nutrients stood out as being correlated to both brain iron concentrations and memory performance: vitamin E, which is found in foods like leafy greens, nuts and vegetable oils; lysine, found in fish, chicken and beef liver; DHA omega-3 fatty acids, from sources like fish and olive, soybean and safflower oils; and LA omega-6 fats, also found in those vegetable oils, as well as almonds and wheatgerm.

The higher people’s intake of those nutrients, the study found, the lower their brain iron concentrations and the better their memory performance.

That was true even when the researchers accounted for participants’ age, exercise habits, alcohol intake and education levels — all of which may affect brain health.

“These are positive results that warrant further inquiry,” said Angel Planells, a Seattle-based registered dietitian who regularly works with older adults.

But Planells, who is also a spokesperson for the Academy of Nutrition & Dietetics, pointed to the wider reality: Most Americans, of all ages, have important nutrient gaps in their diets — typically consuming just one serving of fruits and vegetables a day, for example.

Because people are “creatures of habit,” Planells generally recommends making small, sustainable dietary changes over time, rather than a wholesale makeover: Add a weekly serving of seafood, and have nuts on hand as a snacking option, for example.

Planells added that while diet is key to healthy brain and body aging, there are other factors, too — from physical activity to sleep habits.

“Let’s all age gracefully,” he said, “by eating well, being physically active, staying mentally engaged, making sure our mental health is taken care of, and getting adequate rest and recovery through sleeping.”

Source: HealthDay

Clues to Brain Health May Lie in the Gut

Laura Williamson wrote . . . . . . . . .

Food cravings. Everybody gets them.

Smelling brownies in the oven. Hearing a commercial for a salty chip. Seeing a favorite childhood candy bar at the checkout. They all can awaken memories that drive food cravings.

But what if they also come from a sensory system that has nothing to do with the nose, ears or eyes? A growing body of research says they do. Deep in the gut hides the enteric nervous system, part of the autonomic nervous system that functions independently of the body’s central nervous system, guiding human desires and behaviors. It has more nerve cells than the spinal cord.

Researchers call it “the second brain.”

“The gut, just like the skin or the nose, has a type of cell that recognizes stimuli and discharges electrical pulses,” said Diego Bohórquez, a gut-brain neuroscientist at Duke University School of Medicine in Durham, North Carolina. “And the gut and the brain modulate each other’s functions.”

Bohórquez is one of many neuroscientists, endocrinologists, microbiologists and others looking to the gut to help better understand the brain. Over the past decade, their work has led to the discovery that the gut contains sensors that rapidly send messages to the brain to help it decide what foods to eat, how well to sleep and even whether to feel pain. Researchers are mining the gut-brain connection for its potential to treat a wide range of conditions. Some of them are obviously gut-related – such as obesity and irritable bowel syndrome – but some are far less obvious, such as osteoporosis and post-traumatic stress disorder.

“This is all under development,” said Dr. Michael Gershon, one of the early pioneers in the field of neurogastroenterology. “But it has promise.”

It was the ability of the gut to act without any input from the brain or spinal cord that inspired Gershon to label it “the second brain.” But while the gut, which includes the stomach and intestines, is capable of acting on its own, in practice, communication flows constantly between the two, Gershon said.

“The brain is like the CEO. It sends general instructions to the workers in the gut,” said Gershon, a professor of pathology and cell biology at Columbia University Vagelos College of Physicians and Surgeons in New York City. The workers, however, have a lot of input on how decisions are made, sending information to the brain about what’s going on in their work environment. They gather that information from sensors in the lining of the gut and relay it to the brain through the vagal and spinal nerves.

“Nutrients in specific areas of the gut are feeding information to specific areas of the brain that control pleasure, plus the areas that control sleep or mood,” said Bohórquez, an associate professor of medicine and associate research professor of neurobiology at Duke. His lab and others are investigating whether targeting the gut could influence what happens in the brain.

For example, Bohórquez led a preliminary study uploaded last year to the preprint server BioRxiv showing neuropod cells in the mouse and human gut could instantly distinguish between sugar and non-caloric artificial sweeteners, driving a preference for the caloric over the non-caloric. Understanding how the gut drives the desire to eat sugar is the first step on the road to better methods for preventing obesity and related metabolic conditions, such as Type 2 diabetes, Bohórquez said.

“By knowing the receptors and the cells and the pathways, we can learn how to develop therapies to reduce the craving and constant desire for sugars that eventually lead to metabolic disorders,” he said.

Likewise, gut-related therapies for better mental health are in the nascent stages. The gut produces 95% of the body’s serotonin, known for its role as a mood stabilizer. Researchers are looking into the potential to treat depression and anxiety by targeting serotonin molecules with non-absorbable compounds placed directly into the gut so they reach only the lining of the bowel, something they’ve already accomplished in mice.

That way, treatments for mental health could have fewer side effects, Gershon said. “If you can target drugs to do this, you might be able to have beneficial effects on thinking without systemic effects on other parts of the body.”

Serotonin doesn’t always play a positive role in the gut. Gershon has called it “the sword and the shield of the bowel” because it can do harm as well as good. For example, “too much gut serotonin is bad for bones,” he said.

Popular antidepressants that boost serotonin have been shown to reduce bone density and increase the risk of fractures. Gershon said researchers are investigating whether they might be able to strengthen bones by restricting serotonin in the gut.

Gershon’s work also has led to a better understanding of how serotonin aids communication between the gut and the brain, and its role in digestive processes. This has helped researchers explore ways to treat problems such as irritable bowel syndrome and the nausea associated with chemotherapy.

While researchers continue to search for answers, Gershon advises people follow established guidelines for keeping the gut and the brain in good working order: “Lose weight if you need to and eat lots and lots of fiber to keep the gut going.”

Lifestyle behaviors such as regular physical activity, not smoking and keeping blood pressure, blood sugar and cholesterol levels in the healthy range also help to support good brain health.

Source: American Heart Association

Neuro Surprise: Some Brain Skills Might Improve With Age

Dennis Thompson wrote . . . . . . . . .

There’s an old saying, “Age and guile beat youth and exuberance,” and new research suggests there might be something to that.

Some key brain functions can improve in people as they age, researchers report, challenging the notion that our mental abilities decline across the board as we grow old.

With increasing age, many people appear to get better at focusing on important matters and ignoring distractions — tasks that support other critical brain functions like memory, decision making and self-control, the researchers said.

“This suggests we cannot really speak about aging just as leading to declines in a general sense,” said lead researcher João Veríssimo, an assistant professor at the University of Lisbon in Portugal. “Maybe we need to talk about the precise mental functions that change with aging.”

For this study, Veríssimo’s team looked at three components of mental ability in a group of more than 700 Taiwanese people between 58 and 98 years of age:

  • Alerting, the enhanced vigilance that triggers one’s attention to incoming information.
  • Orienting, the ability to shift brain resources to a particular location in our environment.
  • Executive inhibition, the ability to ignore distractions to focus on what’s important.

“We use all three processes constantly,” Veríssimo explained. “For example, when you are driving a car, alerting is your increased preparedness when you approach an intersection. Orienting occurs when you shift your attention to an unexpected movement, such as a pedestrian. And executive function allows you to inhibit distractions such as birds or billboards so you can stay focused on driving.”

Testing showed that only alerting declined with age among study participants. Both orienting and executive function actually improved until a person’s mid-to-late 70s.

“Those are the abilities I think we really thought declined the most with age. Some things might be more stable, but the past literature has largely suggested these are particularly impaired with age,” said aging expert Angela Gutchess, a professor of psychology at Brandeis University in Waltham, Mass. “This new data really suggests that’s not the case when you look at it more precisely with a larger sample.”

Why can these abilities improve even as your brain ages?

Veríssimo’s team thinks it might come down to experience. You use skills like orienting and executive inhibition your whole life; it makes sense they would improve with lifelong practice, and might even counter some physical effects of aging on the brain.

“Perhaps the practice or accumulation of knowledge that we have with our mental functions throughout our life, perhaps it can counter these declines,” Veríssimo said. “It can lead to the lack of decline and in some cases, according to our results, it may even lead to observable and detectable improvement.”

It also might be that the brain is very good at shifting its resources to support the more crucial mental abilities as we age, Gutchess said.

“The brain imaging literature from the past 25 years or so has really opened up how we think about aging,” she said. “Even in the face of some behavioral declines, you see that the brain is kind of reorganizing and working in different ways in older adults. There’s really malleable, vibrant activity happening under the surface.”

If experience is the key factor, then we might be able to more gracefully age by creating exercises that will help us keep our mental processes sharp, Veríssimo said.

“We know that some of these functions do appear to be susceptible to training,” he said. “We know that if we train people, they can actually get better. It’s conceivable that we could develop targeted interventions that would practice these kind of attentional mechanisms, and this could have downstream effects even for everyday life.”

However, a Georgetown University expert said, we also must acknowledge that all good things come to an end.

No matter how strong our experience, eventually age will win out, said Michael Ullman, director of Georgetown’s Brain and Language Lab, in Washington, D.C.

“Executive function improves until mid-70s, but after that it seems to decline. We think what’s happening is at that point the neurological decline gets faster and faster, and outweighs the previous experience,” Ullman said.

The new study was published in the journal Nature Human Behaviour.

Source: HealthDay

Common Pesticide to Be Banned Over Links to Problems in Children

The Biden Administration said Wednesday that a widely used pesticide will be banned because it’s been linked to neurological damage in children.

The new rule to block the use of chlorpyrifos on food will take effect in six months, the Environmental Protection Agency said.

“Today [the] EPA is taking an overdue step to protect public health,” EPA head Michael Regan said in an agency news release. “Ending the use of chlorpyrifos on food will help to ensure children, farmworkers, and all people are protected from the potentially dangerous consequences of this pesticide.”

Available since the mid-1960s and among the most widely used pesticides, chlorpyrifos is routinely applied to corn, soybeans, apples, broccoli, asparagus and other produce, The New York Times reported.

In April, the Ninth Circuit Court of Appeals told the EPA to stop agricultural use of the pesticide unless it could demonstrate its safety.

The court order gave the EPA a deadline of Aug. 20 to either prove that chlorpyrifos is harmless to children or to end its use on food crops.

“It is very unusual,” Michal Freedhoff, E.P.A. assistant administrator for chemical safety and pollution prevention, said of the court’s directive. “It speaks to the impatience and the frustration that the courts and environmental groups and farmworkers have with the agency.”

“The court basically said, ‘Enough is enough,'” Freedhoff told the Times. “Either tell us that it’s safe, and show your work, and if you can’t, then revoke all tolerances.”

Several states have already banned chlorpyrifos, the Times said.

Studies have linked exposure to the pesticide with lower birth weights, reduced IQs and other developmental problems in children, and a wide range of groups have long fought for a ban on chlorpyrifos, the Times reported.

“It took far too long, but children will no longer be eating food tainted with a pesticide that causes intellectual learning disabilities,” Patti Goldman, an attorney at EarthJustice, told the Times. “Chlorpyrifos will finally be out of our fruits and vegetables.”

Chlorpyrifos can still be used on golf courses, turf, utility poles and fence posts as well as in cockroach bait and ant treatments, the Times reported.

Source: HealthDay