Posts Tagged ‘research’

There are no instant, miracle cures. But recent studies suggest we have more control over our cognitive health than we might think. It just takes some effort.

When it comes to battling dementia, the unfortunate news is this: Medications have proven ineffective at curing or stopping the disease and its most common form, Alzheimer’s disease. But that isn’t the end of the story. According to a recent wave of scientific studies, we have more control over our cognitive health than is commonly known. We just have to take certain steps—ideally, early and often—to live a healthier lifestyle.

In fact, according to a recent report commissioned by the Lancet, a medical journal, around 35% of dementia cases might be prevented if people do things including exercising and engaging in cognitively stimulating activities. “When people ask me how to prevent dementia, they often want a simple answer, such as vitamins, dietary supplements or the latest hyped idea,” says Eric Larson, a physician at Kaiser Permanente in Seattle and one of a group of scientists who helped prepare the report. “I tell them they can take many common-sense actions that promote health throughout life.”

The Lancet report, distilling the findings of hundreds of studies, identifies several factors that likely contribute to dementia risk, many of which can be within people’s power to control. These include midlife obesity, physical inactivity, high blood pressure, Type 2 diabetes, social isolation and low education levels.

Of course, there are no guarantees. Dementia is a complicated disease that has multiple causes and risk factors, some of which remain unknown. Nevertheless, there is increasing evidence that people—even those who inherit genes that put them at greater risk of developing Alzheimer’s in later life—can improve their chances by adopting lifestyle changes.

“It’s not just about running three times a week,” says Sarah Lenz Lock, executive director of AARP’s Global Council on Brain Health. “Instead, it’s about a package of behaviors, including aerobic exercise, strength training, a healthy diet, sleep and cognitive training.”

Because most neurodegenerative diseases take years, if not decades, to develop, researchers say the best time to focus on brain health is long before symptoms occur—ideally by midlife if not before. Still, they emphasize that it is never too late to start.

What follows is a look at what scientific studies tell us about possible ways to reduce dementia risk.

1. Blood-pressure control

The potential role that cardiovascular health—including blood pressure—plays in dementia has been one of the tantalizing highlights of recent research based on the Framingham Heart Study, which has followed thousands of residents of Framingham, Mass., and their relatives since 1948.

The research found a 44% decline in the dementia rate among people age 60 or older for the period 2004 to 2008, compared with 1977 to 1983. Diagnoses fell to two for every 100 study participants from 3.6 in the earlier period. Over the same roughly 30 years, the average age at which dementia was diagnosed rose to 85 from 80.

Co-author Claudia Satizabal, an assistant professor at UT Health San Antonio, says the research suggests that improvements in cardiovascular health and education levels help explain the trend. Improvements in dementia rates have occurred only in participants “who had at least a high-school diploma,” the study says. And as dementia rates have fallen, the study also says, so have the rates of “stroke and other cardiovascular diseases,” thanks in part to a greater use of blood-pressure medication.

Unlike studies in which participants are randomly assigned to different treatment groups and then monitored for results, the Framingham study and others that analyze population data cannot definitively prove a cause-and-effect relationship. Dr. Satizabal says that while the significant decline in dementia rates since 1977 suggests that management of stroke and heart issues could have contributed, that “is something that needs more research.”

A recent study that randomly assigned participants to different treatment goals offers further evidence for the idea that high blood pressure is a treatable risk factor that leads to dementia.

In 2010, researchers at Wake Forest School of Medicine began enrolling almost 9,400 people age 50 and older with high blood pressure in one of two groups. With the aid of medication, one group reduced its systolic blood pressure—which measures pressure in the arteries when the heart contracts—to less than 120. The other group aimed for less than 140.

The group with lower blood pressures experienced such significantly lower rates of death, strokes and heart attacks that in 2015 the researchers stopped the trial ahead of schedule. The scientists concluded it would be unethical to continue because most people should be targeting the lower blood pressure, says the study’s co-author Jeff Williamson, a Wake Forest medical school professor.

In 2017 and 2018, the researchers performed a final round of cognitive tests on participants and discovered that the lower-blood-pressure group had 19% fewer diagnoses of mild cognitive impairment, often a precursor to dementia, and 15% fewer cases of any type of dementia, mild or otherwise.

Using MRIs, the researchers scanned 673 participants’ brains and, upon follow-up, found less damaging changes in the lower-blood-pressure group.

“This is the first trial that has demonstrated an effective strategy for prevention of cognitive impairment,” says Kristine Yaffe, professor of psychiatry, neurology and epidemiology at the University of California, San Francisco. “That’s pretty big news,” says Dr. Yaffe, who wasn’t involved in the study.

2. Exercise

Several studies that have followed large numbers of people for years suggest that physically active individuals are less likely than inactive peers are to develop dementia, according to a recent World Health Organization report.

Exercise increases the flow of blood to the brain, improves the health of blood vessels and raises the level of HDL cholesterol, which together help protect against cardiovascular disease and dementia, says Laura Baker, a professor at Wake Forest School of Medicine. Exercise can also lead to the formation of new brain synapses and protect brain cells from dying.

Prof. Baker’s studies suggest that aerobic exercise can help improve cognitive function in people with mild memory, organizational and attention deficits, which are often the first symptoms of cognitive impairment.

One recent study conducted by Prof. Baker and several co-authors enrolled 65 sedentary adults ages 55 to 89 with mild memory problems. For six months, half completed four 60-minute aerobic-exercise sessions at the gym each week. Under a trainer’s supervision, they exercised mainly on treadmills at 70% to 80% of maximum heart rate. The other half did stretching exercises at 35% of maximum heart rate.

At the beginning and end of the study, researchers collected participants’ blood and spinal fluid and obtained MRI scans of their brains. Over the six months, the aerobic-exercise group had a statistically significant reduction in the level in their spinal fluid of tau protein, which accumulates in the brains of people with Alzheimer’s. They also had increased blood flow to areas of the brain that are important for attention and concentration, and their scores on cognitive tests improved. The stretching group, in contrast, showed no improvement on cognitive tests or tau levels.

3. Cognitive training

Many population studies suggest that education increases cognitive reserve, a term for the brain’s ability to compensate for neurological damage. The Framingham study, for example, found that participants with at least a high-school diploma benefited the most from declining dementia rates, compared with participants with less education.

In another population study, researchers at Columbia University analyzed data from 593 people age 60 or older, 106 of whom developed dementia. People with clerical, unskilled or semiskilled jobs had greater risk of getting the disease than managers and professionals.

In a separate study, some of the same researchers followed 1,772 people age 65 or older, 207 of whom developed dementia. After adjusting the results for age, ethnic group, education and occupation, the authors found that people who engaged in more than six activities a month—including hobbies, reading, visiting friends, walking, volunteering and attending religious services—had a 38% lower rate of developing dementia than people who did fewer activities.

In yet another study, researchers at institutions including Rush University Medical Center’s Rush Institute for Healthy Aging examined the brains of 130 deceased people who had undergone cognitive evaluations when alive. Among individuals in whom similar levels of Alzheimer’s-related brain changes were seen in the postmortem examinations, the researchers found that those who had more education generally had shown higher cognitive function.

Yaakov Stern, a professor at Columbia University College of Physicians and Surgeons who has written about these studies and the impact of education on dementia, recommends maintaining “educational and mentally stimulating activities throughout life.” This fosters growth of new neurons and may slow the rate at which certain regions of the brain shrink with age. It also promotes cognitive reserve, he says.

4. Diet

Efforts to study the impact of diet on dementia are relatively new, but there are some indications that certain diets may be beneficial in lowering the risk of dementia.

Several population studies, for instance, suggest that people with a Mediterranean diet, which is high in fish, fruits, nuts and vegetables, have lower rates of dementia, according to the World Health Organization.

But a variation on that diet may offer even more protection against the development of Alzheimer’s disease, according to a study released in 2015.

In this study, researchers including Dr. Martha Clare Morris, director of the Rush Institute for Healthy Aging, analyzed data from 923 people ages 58 to 98 who kept detailed food diaries about what they ate from 2004 to 2013.

In total, 158 subjects developed dementia. But among individuals who remained cognitively healthy, a high proportion had consumed a diet heavy in leafy green and other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil and wine (in moderation). Their diets were limited in red meat, butter, cheese, sweets and fried and fast foods.

This diet, which researchers named the Mind diet, shares many elements of a Mediterranean diet. But the Mind diet prescribes more foods—including berries and leafy green vegetables—that are associated with lower rates of neurological diseases.

The researchers scored each of the 923 participants on how closely their detailed eating habits followed three diets: Mind, Mediterranean, and Dash diet, designed to reduce high blood pressure. For each diet, researchers ranked the participants based on their scores, subdividing them by the degree to which they followed each diet—closely, partly or little.

This led to several discoveries: First, there were about 50% fewer Alzheimer’s diagnoses among participants who most closely followed either the Mind diet or the Mediterranean diet, compared with those who followed either diet only a little. For the Dash diet, there was a 39% reduction for those who were most faithful to its rules.

Meanwhile, even those who only partly followed the Mind diet saw a 35% reduction in Alzheimer’s diagnoses, while no reduction was seen for those who only partly followed either the Mediterranean or Dash diet.

In contrast to the Mediterranean and Dash diets, “even modest adherence to the Mind diet may have substantial benefits for prevention of Alzheimer’s disease,” says Kristin Gustashaw, a dietitian at Rush.

5. Sleep

No one knows for sure why we sleep. One theory is that sleep helps us remember important information by performing a critical housekeeping function on brain synapses, including eliminating some connections and strengthening others.

Another theory is that sleep washes “toxic substances out of our brains that shouldn’t be there,” including beta amyloid and tau proteins that are implicated in Alzheimer’s, says Ruth Benca, a professor of medicine at the University of California, Irvine.

In a 2015 study, Prof. Benca and others examined 98 participants without dementia ages 50 to 73. Many were at genetic risk for the disease. Brain scans revealed that those reporting more sleep problems had higher levels of amyloid deposits in areas of the brain typically affected by Alzheimer’s.

“Poor sleep may be a risk factor for Alzheimer’s,” says Prof. Benca, who is conducting a study to see whether treating sleep problems may help prevent dementia.

She says sleep—or a lack of it—may help explain why about two-thirds of Alzheimer’s patients are women. Some researchers theorize that during menopause women can become vulnerable to the disease, in part due to increased prevalence of insomnia.

6. Combination

There is a growing consensus that when it comes to preserving brain health, the more healthy habits you adopt, the better.

According to a forthcoming study of 2,765 older adults by researchers at Rush, nonsmokers who stuck to the Mind diet, got regular exercise, engaged in cognitively stimulating activities and drank alcohol in moderation had 60% fewer cases of dementia over six years than people with just one such habit.

A study published in July found that people at greater genetic risk for Alzheimer’s appear to benefit just as much from eating well, exercising and drinking moderately as those who followed the same habits but weren’t at elevated genetic risk for the disease.

The study, by researchers including Kenneth Langa, associate director of the Institute of Gerontology at the University of Michigan, examined data from 196,383 Britons age 60 and older. Over about a decade, there were 38% fewer dementia diagnoses among individuals who had healthy habits and a gene, APOE4, that puts people at higher risk for Alzheimer’s, than there were among people who had the gene and poor habits. The gene increases the risk for Alzheimer’s by two to 12 times, depending on how many copies a person has.

Among participants with low genetic risk for Alzheimer’s, healthy habits were associated with a 40% reduction in the incidence of the disease. The results suggest a correlation between lifestyle, genetic risk and dementia, the study says.

Many point to a recent clinical trial in Finland of 1,260 adults ages 60 to 77 as proof that a multipronged approach can work.

The researchers, from institutions including the Karolinska Institute in Sweden and the National Institute for Health and Welfare in Helsinki, randomly assigned half of the participants, all deemed at high risk for dementia, to regular sessions with nutritionists, exercise trainers and instructors in computerized brain-training programs. The participants attended social events and were closely monitored for conditions including high blood pressure, excess abdominal weight and high blood sugar.

“They got support from each other to make lifestyle changes,” says co-author Miia Kivipelto, a professor at the Karolinska Institute in Sweden.

The other half received only general health advice.

After two years, both groups showed improvements in cognitive performance. But the overall scores of the intensive-treatment group improved by 25% more than the scores for the other group. The intensive-treatment group scored between 40% and 150% better on tests of executive function, mental speed and complex memory tasks, suggesting that a multifaceted approach can “improve or maintain cognitive functioning in at-risk elderly people,” the study says.

“We are studying whether exercise and lifestyle can be medicine to protect brain health as we get older,” says Prof. Baker, who is overseeing a U.S. study modeled on the Finnish trial.

https://apple.news/AzlC5CLNvQJWJrsP-qrJFIw

By Rory Sullivan

Although hiccups seem a nuisance, scientists have discovered they may play a crucial role in our development — by helping babies to regulate their breathing.

In a study led by University College London (UCL), researchers monitoring 13 newborn babies found that hiccupping triggered a large wave of brain signals which could aid their development.

Lorenzo Fabrizi, the study’s senior author, said in a statement that this brain activity might help babies “to learn how to monitor the breathing muscles,” eventually leading to an ability to control breathing voluntarily.

He added: “When we are born, the circuits which process body sensations are not fully developed, so the establishment of such networks is a crucial developmental milestone for newborns.”

Since the babies involved in the study were pre-term and full-term, ranging from 30 to 42 weeks gestational age, the scientists believe this development could be typical of the final trimester of pregnancy.

According to the researchers, fetuses and newborn infants often hiccup.

The phenomenon is seen as early as nine weeks into pregnancy, and pre-term infants — those born at least three weeks premature — spend approximately 15 minutes hiccupping every day.

The pre-term and full-term newborns involved in the study had electrodes placed on their scalps and sensors on their torsos to monitor for hiccups.

Scientists found that contractions in the babies’ diaphragms produced three brainwaves, and believe that through the third brainwave babies may be able to link the ‘hic’ sound of the hiccup to the physical contraction they feel.

Kimberley Whitehead, the study’s lead author, told CNN: “The muscle contraction of a hiccup is quite big — it’s good for the developing brain because it suddenly gives a big boost of input, which helps the brain cells to all link together for representing that particular body part.”

She added that hiccups have no known advantage for adults, and suggested they could be an example of “a hangover from early periods of our life that persists into later life.”

The same researchers have previously theorized that a baby’s kicks in the womb may help it to create a mental map of its own body.

Their new findings may show the same process occurring internally.

https://www.cnn.com/2019/11/12/health/babies-hiccup-wellness-scli-intl-scn/index.html?utm_source=The+Good+Stuff&utm_campaign=2aa589d67e-EMAIL_CAMPAIGN_2019_11_14_08_33&utm_medium=email&utm_term=0_4cbecb3309-2aa589d67e-103653961

By Julie Zaugg and Jared Peng

Authorities in China have approved a drug for the treatment of Alzheimer’s disease, the first new medicine with the potential to treat the cognitive disorder in 17 years.

The seaweed-based drug, called Oligomannate, can be used for the treatment of mild to moderate Alzheimer’s, according to a statement from China’s drug safety agency. The approval is conditional however, meaning that while it can go on sale during additional clinical trials, it will be strictly monitored and could be withdrawn should any safety issues arise.

In September, the team behind the new drug, led by Geng Meiyu at the Shanghai Institute of Materia Medica under the Chinese Academy of Sciences, said they were inspired to look into seaweed due to the relatively low incidence of Alzheimer’s among people who consume it regularly.

In a paper in the journal Cell Research, Geng’s team described how a sugar contained within seaweed suppresses certain bacteria contained in the gut which can cause neural degeneration and inflammation of the brain, leading to Alzheimer’s.

This mechanism was confirmed during a clinical trial carried out by Green Valley, a Shanghai-based pharmaceutical company that will be bringing the new drug to market.

Conducted on 818 patients, the trial found that Oligomannate — which is derived from brown algae — can statistically improve cognitive function among people with Alzheimer’s in as little as four weeks, according to a statement from Green Valley.

“These results advance our understanding of the mechanisms that play a role in Alzheimer’s disease and imply that the gut microbiome is a valid target for the development of therapies,” neurologist Philip Scheltens, who advises Green Valley and heads the Alzheimer Center Amsterdam, said in the statement.

Vincent Mok, who heads the neurology division at the Chinese University of Hong Kong, said the new drug showed “encouraging results” when compared to acetylcholinesterase inhibitors — the existing treatment for mild to severe Alzheimer’s.

“It is just as effective but it has fewer side effects,” he told CNN. “It will also open up new avenues for Alzheimer’s research, focusing on the gut microbiome.”

Since very little is known about the mechanisms of the new drug, Mok said it should also be probed to see if it could have a protective effect and possibly slow down the progression of the disease in patients who have yet to develop strong symptoms of dementia.

The company said Oligomannate will be available in China “very soon,” and it is currently seeking approval to market it abroad, with plans to launch third-phase clinical trials in the US and Europe in early 2020.

Alzheimer’s disease, which starts with memory loss and escalates to severe brain damage, is believed to cause 60% to 70% of the cases of dementia reported worldwide, according to the World Health Organization. Dementia affects an estimated 50 million people worldwide, including 9.5 million people in mainland China, Hong Kong and Taiwan.

Named after Alois Alzheimer, the neuropathologist who discovered the disease in 1906, it has so far confounded researchers and pharmaceutical companies.

In October, US pharmaceutical giant Biogen said it would pursue Food and Drug Administration (FDA) approval for an experimental treatment called aducanumab, after announcing in March it was canceling a large clinical trial for the drug.

Johnson & Johnson, Merck, Pfizer and Eli Lilly have all previously abandoned projects to develop a drug for Alzheimer’s after unsatisfactory clinical data.

https://www.cnn.com/2019/11/03/health/china-alzheimers-drug-intl-hnk-scli/index.html


Laboratory animals such as mice are an important part of chemical safety tests, say researchers

by Jeff Tollefson

The US Environmental Protection Agency (EPA) is trying to sharply reduce its use of animals in toxicity tests. Many scientists and environmentalists say the move is premature and could undermine chemical regulation.

In a memo to staff, EPA administrator Andrew Wheeler said that the agency would make use of “cutting-edge, ethically sound science” that does not rely on animal testing.

Wheeler signed a directive on 10 September that commits the EPA to reduce its funding request for animal studies by 30% by 2025, and to phase them out entirely by 2035. After 2035, any tests or funds for studies involving animals such as mice would require the approval of the EPA administrator. The plan, which will affect research by EPA scientists and industry, has been in the works for more than a year. Agency officials have said that the shift away from animal experiments won’t limit chemical regulation or reduce public safety.

Wheeler also said that EPA had awarded US$4.25 million in grants to universities for research into alternative toxicity testing methods. The grant recipients are Johns Hopkins University in Baltimore, Maryland; Vanderbilt University in Nashville, Tennessee; Oregon State University in Corvallis; and the University of California, Riverside.

“I don’t think anyone would be saddened by reducing animal research,” says Laura Vandenberg, an environmental health scientist at the University of Massachusetts Amherst. But she fears that the EPA is effectively tying its own hands.

Uncertain outcomes

Scientists can and do use advanced screening tools to study the potential effects of chemicals at the cellular and biochemical level, Vandenberg says. But to regulate a chemical, the EPA must show that there are adverse effects in living organisms, she says. “There is no adverse effect in a Petri dish.”

And just because researchers don’t see negative effects of chemicals on cells in the lab, it doesn’t mean that they aren’t there, Vandenberg adds. “We are going to get caught in a position where we won’t really be able to regulate chemicals in the US.”

The Humane Society of the United States, an animal-advocacy group in Washington DC, praised the EPA’s decision. “We applaud the agency and urge industry and other stakeholders to continue this momentum and move away from animal testing,” said chief executive officer Kitty Block in a statement.

Not everyone is so sanguine about EPA’s decision. The move represents an “unholy alliance” between the chemical industry and animal-rights groups that are pushing to halt animal tests, says Jennifer Sass, a senior scientist at the Natural Resources Defense Council, an environmental advocacy group in New York City.

Sass says that the EPA has reduced its reliance on animal testing in certain areas. For instance, tests to see whether a chemical is corrosive to the skin can now be done on skin that is grown in a Petri dish. But without tests on animals such as mice or rabbits, the only way for companies to study chemical interactions in the body is to use computer models, she says. And those models are often proprietary, which makes it hard to assess their accuracy.

“A chemical goes into a black box, and out comes an answer that is very hard for people to understand and independently review,” Sass says.

https://www.nature.com/articles/d41586-019-02715-0?utm_source=Nature+Briefing&utm_campaign=c98b98c2f6-briefing-dy-20190910_COPY_01&utm_medium=email&utm_term=0_c9dfd39373-c98b98c2f6-44039353

Doctors have newly outlined a type of dementia that could be more common than Alzheimer’s among the oldest adults, according to a report published Tuesday in the journal Brain.

The disease, called LATE, may often mirror the symptoms of Alzheimer’s disease, though it affects the brain differently and develops more slowly than Alzheimer’s. Doctors say the two are frequently found together, and in those cases may lead to a steeper cognitive decline than either by itself.

In developing its report, the international team of authors is hoping to spur research — and, perhaps one day, treatments — for a disease that tends to affect people over 80 and “has an expanding but under-recognized impact on public health,” according to the paper.

“We’re really overhauling the concept of what dementia is,” said lead author Dr. Peter Nelson, director of neuropathology at the University of Kentucky Medical Center.

Still, the disease itself didn’t come out of the blue. The evidence has been building for years, including reports of patients who didn’t quite fit the mold for known types of dementia such as Alzheimer’s.

“There isn’t going to be one single disease that is causing all forms of dementia,” said Sandra Weintraub, a professor of psychiatry, behavioral sciences and neurology at Northwestern University Feinberg School of Medicine. She was not involved in the new paper.

Weintraub said researchers have been well aware of the “heterogeneity of dementia,” but figuring out precisely why each type can look so different has been a challenge. Why do some people lose memory first, while others lose language or have personality changes? Why do some develop dementia earlier in life, while others develop it later?

Experts say this heterogeneity has complicated dementia research, including Alzheimer’s, because it hasn’t always been clear what the root cause was — and thus, if doctors were treating the right thing.

What is it?

The acronym LATE stands for limbic-predominant age-related TDP-43 encephalopathy. The full name refers to the area in the brain most likely to be affected, as well as the protein at the center of it all.

“These age-related dementia diseases are frequently associated with proteinaceous glop,” Nelson said. “But different proteins can contribute to the glop.”

In Alzheimer’s, you’ll find one set of glops. In Lewy body dementia, another glop.

And in LATE, the glop is a protein called TDP-43. Doctors aren’t sure why the protein is found in a modified, misfolded form in a disease like LATE.

“TDP-43 likes certain parts of the brain that the Alzheimer’s pathology is less enamored of,” explained Weintraub, who is also a member of Northwestern’s Mesulam Center for Cognitive Neurology and Alzheimer’s Disease.

“This is an area that’s going to be really huge in the future. What are the individual vulnerabilities that cause the proteins to go to particular regions of the brain?” she said. “It’s not just what the protein abnormality is, but where it is.”

More than a decade ago, doctors first linked the TDP protein to amyotrophic lateral sclerosis, otherwise known as ALS or Lou Gehrig’s disease. It was also linked to another type of dementia, called frontotemporal lobar degeneration.

LATE “is a disease that’s 100 times more common than either of those, and nobody knows about it,” said Nelson.

The new paper estimates, based on autopsy studies, that between 20 and 50% of people over 80 will have brain changes associated with LATE. And that prevalence increases with age.

Experts say nailing down these numbers — as well as finding better ways to detect and research the disease — is what they hope comes out of consensus statements like the new paper, which gives scientists a common language to discuss it, according to Nelson.

“People have, in their own separate bailiwicks, found different parts of the elephant,” he said. “But this is the first place where everybody gets together and says, ‘This is the whole elephant.’ ”

What this could mean for Alzheimer’s

The new guidelines could have an impact on Alzheimer’s research, as well. For one, experts say some high-profile drug trials may have suffered as a result of some patients having unidentified LATE — and thus not responding to treatment.

In fact, Nelson’s colleagues recently saw that firsthand: a patient, now deceased, who was part of an Alzheimer’s drug trial but developed dementia anyway.

“So, the clinical trial was a failure for Alzheimer’s disease,” Nelson said, “but it turns out he didn’t have Alzheimer’s disease. He had LATE.”

Nina Silverberg, director of the Alzheimer’s Disease Research Centers Program at the National Institute on Aging, said she suspects examples like this are not the majority — in part because people in clinical trials tend to be on the younger end of the spectrum.

“I’m sure it plays some part, but maybe not as much as one might think at first,” said Silverberg, who co-chaired the working group that led to the new paper.

Advances in testing had already shown that some patients in these trials lacked “the telltale signs of Alzheimer’s,” she said.

In some cases, perhaps it was LATE — “and it’s certainly possible that there are other, as yet undiscovered, pathologies that people may have,” she added.

“We could go back and screen all the people that had failed their Alzheimer’s disease therapies,” Nelson said. “But what we really need to do is go forward and try to get these people out of the Alzheimer’s clinical trials — and instead get them into their own clinical trials.”

Silverberg describes the new paper as “a roadmap” for research that could change as we come to discover more about the disease. And researchers can’t do it without a large, diverse group of patients, she added.

“It’s probably going to take years and research participants to help us understand all of that,” she said.

https://www.cnn.com/2019/04/30/health/dementia-late-alzheimers-study/index.html


Two-photon imaging shows neurons firing in a mouse brain. Recordings like this enable researchers to track which neurons are firing, and how they potentially correspond to different behaviors. The image is credited to Yiyang Gong, Duke University.

Summary: Convolutional neural network model significantly outperforms previous methods and is as accurate as humans in segmenting active and overlapping neurons.

Source: Duke University

Biomedical engineers at Duke University have developed an automated process that can trace the shapes of active neurons as accurately as human researchers can, but in a fraction of the time.

This new technique, based on using artificial intelligence to interpret video images, addresses a critical roadblock in neuron analysis, allowing researchers to rapidly gather and process neuronal signals for real-time behavioral studies.

The research appeared this week in the Proceedings of the National Academy of Sciences.

To measure neural activity, researchers typically use a process known as two-photon calcium imaging, which allows them to record the activity of individual neurons in the brains of live animals. These recordings enable researchers to track which neurons are firing, and how they potentially correspond to different behaviors.

While these measurements are useful for behavioral studies, identifying individual neurons in the recordings is a painstaking process. Currently, the most accurate method requires a human analyst to circle every ‘spark’ they see in the recording, often requiring them to stop and rewind the video until the targeted neurons are identified and saved. To further complicate the process, investigators are often interested in identifying only a small subset of active neurons that overlap in different layers within the thousands of neurons that are imaged.

This process, called segmentation, is fussy and slow. A researcher can spend anywhere from four to 24 hours segmenting neurons in a 30-minute video recording, and that’s assuming they’re fully focused for the duration and don’t take breaks to sleep, eat or use the bathroom.

In contrast, a new open source automated algorithm developed by image processing and neuroscience researchers in Duke’s Department of Biomedical Engineering can accurately identify and segment neurons in minutes.

“As a critical step towards complete mapping of brain activity, we were tasked with the formidable challenge of developing a fast automated algorithm that is as accurate as humans for segmenting a variety of active neurons imaged under different experimental settings,” said Sina Farsiu, the Paul Ruffin Scarborough Associate Professor of Engineering in Duke BME.

“The data analysis bottleneck has existed in neuroscience for a long time — data analysts have spent hours and hours processing minutes of data, but this algorithm can process a 30-minute video in 20 to 30 minutes,” said Yiyang Gong, an assistant professor in Duke BME. “We were also able to generalize its performance, so it can operate equally well if we need to segment neurons from another layer of the brain with different neuron size or densities.”

“Our deep learning-based algorithm is fast, and is demonstrated to be as accurate as (if not better than) human experts in segmenting active and overlapping neurons from two-photon microscopy recordings,” said Somayyeh Soltanian-Zadeh, a PhD student in Duke BME and first author on the paper.

Deep-learning algorithms allow researchers to quickly process large amounts of data by sending it through multiple layers of nonlinear processing units, which can be trained to identify different parts of a complex image. In their framework, this team created an algorithm that could process both spatial and timing information in the input videos. They then ‘trained’ the algorithm to mimic the segmentation of a human analyst while improving the accuracy.

The advance is a critical step towards allowing neuroscientists to track neural activity in real time. Because of their tool’s widespread usefulness, the team has made their software and annotated dataset available online.

Gong is already using the new method to more closely study the neural activity associated with different behaviors in mice. By better understanding which neurons fire for different activities, Gong hopes to learn how researchers can manipulate brain activity to modify behavior.

“This improved performance in active neuron detection should provide more information about the neural network and behavioral states, and open the door for accelerated progress in neuroscience experiments,” said Soltanian-Zadeh.

https://neurosciencenews.com/artificial-intelligence-neurons-11076/

By Emily Underwood

One of the thorniest debates in neuroscience is whether people can make new neurons after their brains stop developing in adolescence—a process known as neurogenesis. Now, a new study finds that even people long past middle age can make fresh brain cells, and that past studies that failed to spot these newcomers may have used flawed methods.

The work “provides clear, definitive evidence that neurogenesis persists throughout life,” says Paul Frankland, a neuroscientist at the Hospital for Sick Children in Toronto, Canada. “For me, this puts the issue to bed.”

Researchers have long hoped that neurogenesis could help treat brain disorders like depression and Alzheimer’s disease. But last year, a study in Nature reported that the process peters out by adolescence, contradicting previous work that had found newborn neurons in older people using a variety of methods. The finding was deflating for neuroscientists like Frankland, who studies adult neurogenesis in the rodent hippocampus, a brain region involved in learning and memory. It “raised questions about the relevance of our work,” he says.

But there may have been problems with some of this earlier research. Last year’s Nature study, for example, looked for new neurons in 59 samples of human brain tissue, some of which came from brain banks where samples are often immersed in the fixative paraformaldehyde for months or even years. Over time, paraformaldehyde forms bonds between the components that make up neurons, turning the cells into a gel, says neuroscientist María Llorens-Martín of the Severo Ochoa Molecular Biology Center in Madrid. This makes it difficult for fluorescent antibodies to bind to the doublecortin (DCX) protein, which many scientists consider the “gold standard” marker of immature neurons, she says.

The number of cells that test positive for DCX in brain tissue declines sharply after just 48 hours in a paraformaldehyde bath, Llorens-Martín and her colleagues report today in Nature Medicine. After 6 months, detecting new neurons “is almost impossible,” she says.

When the researchers used a shorter fixation time—24 hours—to preserve donated brain tissue from 13 deceased adults, ranging in age from 43 to 87, they found tens of thousands of DCX-positive cells in the dentate gyrus, a curled sliver of tissue within the hippocampus that encodes memories of events. Under a microscope, the neurons had hallmarks of youth, Llorens-Martín says: smooth and plump, with simple, undeveloped branches.

In the sample from the youngest donor, who died at 43, the team found roughly 42,000 immature neurons per square millimeter of brain tissue. From the youngest to oldest donors, the number of apparent new neurons decreased by 30%—a trend that fits with previous studies in humans showing that adult neurogenesis declines with age. The team also showed that people with Alzheimer’s disease had 30% fewer immature neurons than healthy donors of the same age, and the more advanced the dementia, the fewer such cells.

Some scientists remain skeptical, including the authors of last year’s Nature paper. “While this study contains valuable data, we did not find the evidence for ongoing production of new neurons in the adult human hippocampus convincing,” says Shawn Sorrells, a neuroscientist at the University of Pittsburgh in Pennsylvania who co-authored the 2018 paper. One critique hinges on the DCX stain, which Sorrells says isn’t an adequate measure of young neurons because the DCX protein is also expressed in mature cells. That suggests the “new” neurons the team found were actually present since childhood, he says. The new study also found no evidence of pools of stem cells that could supply fresh neurons, he notes. What’s more, Sorrells says two of the brain samples he and his colleagues looked at were only fixed for 5 hours, yet they still couldn’t find evidence of young neurons in the hippocampus.

Llorens-Martín says her team used multiple other proteins associated with neuronal development to confirm that the DCX-positive cells were actually young, and were “very strict,” in their criteria for identifying young neurons.

Heather Cameron, a neuroscientist at the National Institute of Mental Health in Bethesda, Maryland, remains persuaded by the new work. Based on the “beauty of the data” in the new study, “I think we can all move forward pretty confidently in the knowledge that what we see in animals will be applicable in humans, she says. “Will this settle the debate? I’m not sure. Should it? Yes.”

https://www.sciencemag.org/news/2019/03/new-neurons-life-old-people-can-still-make-fresh-brain-cells-study-finds?utm_campaign=news_daily_2019-03-25&et_rid=17036503&et_cid=2734364