Posts Tagged ‘brain’

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

Scientists have peered inside the brain to show how taking DMT affects human consciousness by significantly altering the brain’s electrical activity.

DMT (or dimethyltryptamine) is one of the main psychoactive constituents in ayahuasca, the psychedelic brew traditionally made from vines and leaves of the Amazon rainforest. The drink is typically prepared as part of a shamanic ceremony and associated with unusual and vivid visions or hallucinations.

The latest study is the first to show how the potent psychedelic changes our waking brain waves – with researchers comparing its powerful effects to ‘dreaming while awake’.

The work, led by researchers from the Centre for Psychedelic Research at Imperial College London and published today in the journal Scientific Reports, may help to explain why people taking DMT and ayahuasca experience intense visual imagery and immersive ‘waking-dream’ like experiences.

DMT is a naturally occurring chemical found in miniscule amounts in the human brain but also in larger amounts in a number of plant species around the world.

Accounts from people who have taken DMT report intense visual hallucinations often accompanied by strong emotional experiences and even ‘breakthroughs’ into what users describe as an alternate reality or dimension.

But scientists are interested in using the powerful psychoactive compound for research as it produces relatively short but intense psychedelic experiences, providing a window for collecting data on brain activity when consciousness is profoundly altered.

In the latest study, the Imperial team captured EEG measures from healthy participants in a clinical setting, in a placebo-controlled design.

A total of 13 participants were given an intravenous infusion of DMT at the National Institute for Health Research (NIHR) Imperial Clinical Research Facility.

Volunteers were fitted with caps with electrodes to measure the brain’s electrical activity, before, during and after their infusion, with the peak of the psychedelic experience lasting around 10 minutes.

Analysis revealed that DMT significantly altered electrical activity in the brain, characterised by a marked drop off in alpha waves – the human brain’s dominant electrical rhythm when we are awake. They also found a short-lived increase in brainwaves typically associated with dreaming, namely, theta waves.

In addition to changes in the types of brainwaves, they also found that, overall, brain activity became more chaotic and less predictable – the opposite to what is seen in states of reduced consciousness, such as in deep sleep or under general anaesthesia.

“The changes in brain activity that accompany DMT are slightly different from what we see with other psychedelics, such as psilocybin or LSD, where we see mainly only reductions in brainwaves,” said lead author Christopher Timmermann, from the Centre for Psychedelic Research.

“Here we saw an emergent rhythm that was present during the most intense part of the experience, suggesting an emerging order amidst the otherwise chaotic patterns of brain activity. From the altered brainwaves and participants’ reports, it’s clear these people are completely immersed in their experience – it’s like daydreaming only far more vivid and immersive, it’s like dreaming but with your eyes open.”

Mr Timmermann explains that while it’s unclear as to whether DMT may have any clinical potential at this stage, the group hopes to take the work further by delivering a continuous infusion of DMT to extend the window of the psychedelic experience and collect more data.

The team says future studies could include more sophisticated measurements of brain activity, such as fMRI, to show which regions and networks of the brain are affected by DMT. They believe the visual cortex, the large area towards the back of the brain, is likely to be involved.

Dr Robin Carhart-Harris, head of Centre for Psychedelic Research, said: “DMT is a particularly intriguing psychedelic. The visual vividness and depth of immersion produced by high-doses of the substance seems to be on a scale above what is reported with more widely studied psychedelics such as psilocybin or ‘magic mushrooms’.

“It’s hard to capture and communicate what it is like for people experiencing DMT but likening it to dreaming while awake or a near-death experience is useful.

“Our sense it that research with DMT may yield important insights into the relationship between brain activity and consciousness, and this small study is a first step along that road.”

https://www.eurekalert.org/pub_releases/2019-11/icl-acc111819.php

New research has found that people who are illiterate, meaning they never learned to read or write, may have nearly three times greater risk of developing dementia than people who can read and write. The study is published in the November 13, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

According to the United States Department of Education, approximately 32 million adults in the country are illiterate.

“Being able to read and write allows people to engage in more activities that use the brain, like reading newspapers and helping children and grandchildren with homework,” said study author Jennifer J. Manly, Ph.D., of Columbia University Vagelos College of Physicians and Surgeons in New York. “Previous research has shown such activities may reduce the risk of dementia. Our new study provides more evidence that reading and writing may be important factors in helping maintain a healthy brain.”

The study looked at people with low levels of education who lived in northern Manhattan. Many were born and raised in rural areas in the Dominican Republic where access to education was limited. The study involved 983 people with an average age of 77. Each person went to school for four years or less. Researchers asked each person, “Did you ever learn to read or write?” Researchers then divided people into two groups; 237 people were illiterate and 746 people were literate.

Participants had medical exams and took memory and thinking tests at the beginning of the study and at follow-up appointments that occurred every 18 months to two years. Testing included recalling unrelated words and producing as many words as possible when given a category like fruit or clothing.

Researchers found of the people who were illiterate, 83 of 237 people, or 35 percent, had dementia at the start of the study. Of the people who were literate, 134 of 746 people, or 18 percent, had dementia. After adjusting for age, socioeconomic status and cardiovascular disease, people who could not read and write had nearly a three times greater chance of having dementia at the start of the study.

Among participants without dementia at the start of the study, during follow-up an average of four years later, 114 of 237 people who were illiterate, or 48 percent, had dementia. Of the people who were literate, 201 of 746 people, or 27 percent, had dementia. After adjusting for age, socioeconomic status and cardiovascular disease, researchers found that people who could not read and write were twice as likely to develop dementia during the study.

When researchers evaluated language, speed, spatial, and reasoning skills, they found that adults who were illiterate had lower scores at the start of the study. But their test scores did not decline at a more rapid rate as the study progressed.

“Our study also found that literacy was linked to higher scores on memory and thinking tests overall, not just reading and language scores,” said Manly. “These results suggest that reading may help strengthen the brain in many ways that may help prevent or delay the onset of dementia.”

Manly continued, “Even if they only have a few years of education, people who learn to read and write may have lifelong advantages over people who never learn these skills.”

Manly said future studies should find out if putting more resources into programs that teach people to read and write help reduce the risk of dementia.

A limitation of the study was that researchers did not ask how or when literate study participants learned to read and write.

The study was supported by the National Institutes of Health and National Institute on Aging.

Story Source:

Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

Journal Reference:

Miguel Arce Rentería, Jet M.J. Vonk, Gloria Felix, Justina F. Avila, Laura B. Zahodne, Elizabeth Dalchand, Kirsten M. Frazer, Michelle N. Martinez, Heather L. Shouel, Jennifer J. Manly. Illiteracy, dementia risk, and cognitive trajectories among older adults with low education. Neurology, 2019; 10.1212/WNL.0000000000008587 DOI: 10.1212/WNL.0000000000008587

https://www.sciencedaily.com/releases/2019/11/191114180033.htm

By Kristin Houser

Down syndrome is a cognitive disability that can affect a person’s memory or ability to learn — intellectual impairments researchers traditionally thought were untreatable and irreversible.

But now, researchers from the University of California San Francisco and Baylor College of Medicine say they’ve reversed the impairments in mouse models of Down syndrome — potentially foreshadowing an ethically-fraught future in which doctors can do the same for humans with the condition.

All people with Down syndrome share one thing in common: an extra copy of chromosome 21. For that reason, much of the research on Down syndrome has focused on genetics.

But for this new study, published Friday in the prestigious journal Science, researchers focused on the protein-producing cells in the brains of mice with Down syndrome. That led them to the discovery that the animals’ hippocampus regions produced 39 percent less protein than those of typical mice.

Further study led the researchers to conclude that the presence of an extra chromosome likely prompted the animals’ hippocampal cells to trigger the integrated stress response (ISR), which decreased protein production.

“The cell is constantly monitoring its own health,” researcher Peter Walter said in a press release. “When something goes wrong, the cell responds by making less protein, which is usually a sound response to cellular stress. But you need protein synthesis for higher cognitive functions, so when protein synthesis is reduced, you get a pathology of memory formation.”

By blocking the activity of PKR, the enzyme that prompted the ISR in the mouse model’s hippocampal cells, the researchers found they could not only reverse the decreased protein production but also improve the animals’ cognitive function.

Of course, just because something works in mice doesn’t mean it’ll work in humans.

However, when the researchers analyzed postmortem brain tissue samples of people with Down syndrome, they found evidence that the ISR had been activated. They also obtained a tissue sample from a person with Down syndrome who only had the extra copy of chromosome 21 in some of their cells — and those cells were the only ones with ISR activated.

“We started with a situation that looked hopeless,” Walter said. “Nobody thought anything could be done. But we may have struck gold.”

https://futurism.com/neoscope/scientists-reverse-cognitive-deficiets-of-down-syndrome-mice

Thanks to Kebmodee for bringing this to the It’s Interesting community.

by NICOLETTA LANESE

Kent Kiehl and his research team regularly park their long, white trailer just outside the doors of maximum-security prisons across the US. Inside the vehicle sits the bulky body of a mobile MRI machine. During each visit, people from the prison make their way to and from the vehicle in hourly shifts to have their brains scanned and help to answer an age-old question: What makes a murderer?

“It’s not an uncommon thing for [incarcerated people], while they’re getting a scan, to be like, ‘I’ve always been different. Can you tell me why I’ve always been so different?’” says Kiehl, a neuroscientist at the University of New Mexico and the Albuquerque-based nonprofit Mind Research Network (MRN) who helped design the mobile MRI system back in the early 2000s.


SCAN-MOBILE: Kiehl and his colleagues made more than 75 modifications to a trailer and the MRI system inside to outfit both for the team’s unique research.

The author of The Psychopath Whisperer: The Science of Those Without a Conscience, Kiehl has been fascinated by the criminal mind since he was an undergraduate at the University of California, Davis. Now, as director of mobile imaging at MRN, he oversees efforts to gather brain scans from thousands of people held in US prisons to learn what features, if any, might differ from scans of the general population.

This massive dataset recently allowed Kiehl to examine the brain structures of more than 800 men held in state prisons in New Mexico and Wisconsin in an attempt to distinguish incarcerated people who have committed homicide from those who have committed other crimes.

First, Kiehl and his colleagues laboriously sorted the pool of people who had volunteered for the study into three categories based on their crimes: homicide, violent offenses that were not homicide, or non-violent or minimally violent transgressions. The team relied on official convictions, self-reported homicides, and confidential interviews with participants to determine who attempted or committed murder—both offenses that got a “homicide” label in their dataset.

People charged with felony murder—meaning that they had committed a serious felony that was in some way connected to a person’s death, even though they hadn’t intended to kill the victim—and people whose cases indicated considerable doubt about a judgment of homicide were not counted among murderers. And occasionally, people were moved from another category into the homicide group, Kiehl says. The researchers excluded people with abnormal radiology reports, traumatic brain injury, or diagnosed psychotic disorders from the study.

Controlling for substance use severity, time in prison, age, and IQ, the team analyzed the MRI data to look for differences among the study participants. Compared with the other two groups, the 200 men who had committed homicide showed significantly reduced gray matter in several brain regions that play important roles in behavioral control and social cognition.

“I think that the intriguing thing was, first, that they found a difference,” says Hannes Vogel, a neuropathologist at Stanford University Medical Center who was not involved in the work. “And second of all, that it correlates with some of the brain centers that deal with behavior and social interaction.”

Lora Cope, a neuroscientist who studies substance disorders at the University of Michigan, notes in an email to The Scientist that the team’s mobile MRI system has now been used in correctional facilities all over New Mexico and Wisconsin, and “has really revolutionized this area of research.” Indeed, the MRN has now used the equipment to collect roughly 6,500 scans from more than 3,000 research participants since its first outing in 2007.

Although Cope wasn’t involved in the current project, she worked with Kiehl a few years ago while earning her doctorate at the University of New Mexico. After speaking with members of the Avielle Foundation, named for a six-year-old victim of the 2012 Sandy Hook Elementary School shooting, the two researchers spearheaded a study of more than 150 incarcerated young males, 20 of whom had been convicted of homicide, held at a maximum-security detention facility within the state. “Jeremy, [Avielle’s] father, really wanted to know if there was anything neuroscience could tell us about boys who commit homicide,” says Kiehl.

As in the current study, Cope and Kiehl deployed the mobile scanner to collect MRI scans of the incarcerated teens in New Mexico and discovered differences between those who had committed homicide and their imprisoned peers. The homicide offenders “had significantly less gray matter volume in parts of their temporal lobes,” Cope says. When Kiel compared the data from that study with the results of his latest project, he found a high degree of overlap. “Lo and behold . . . we found and replicated every region that was different in the boys and was different in the adult males, and in the same way,” he says.

The latest study’s finding that MRI data can distinguish homicide offenders not only from people who committed non-violent crimes, but also from those who performed other violent crimes, is particularly interesting, says Harold Koenigsberg, a psychiatrist at Icahn School of Medicine at Mount Sinai. “I would have thought there would be more of an overlap between [homicide and violent non-homicide offenders],” he says. “I’m surprised that it was so specific to homicide.”


ANATOMY OF A MURDERER: Homicide offenders exhibited reduced gray matter density compared with other violent offenders in the regions of the brain highlighted blue and green above.

Koenigsberg notes that homicidal violence can itself be split into two categories: impulsive and instrumental. Impulsive violence is born of unbridled emotions and overblown reactions, a brand of behavior linked to poor frontal lobe functioning and abnormal serotonin levels. Instrumental violence, on the other hand, is premeditated and is associated with other brain changes, such as reduced amygdala activation during emotion processing. “These two groups, we think that they have different biologies,” says Koenigsberg. Kiehl’s dataset could be enriched by adding measures of neurotransmitter release and electrical activity, along with related behavioral assessments, he suggests, and with both functional and structural data, psychologists might learn more about what gives rise to these distinct behavioral phenotypes.

Koenigsberg, Vogel, and Kiehl all note that the structural data collected in the current study cannot on its own be used to predict who has committed homicide, let alone who might in the future. Nonetheless, the paper may find its way into the courtroom, says Vogel. If lawyers felt so inclined, they could try to “find an expert on one side who will quote this [paper]” in defense of someone who has committed a homicide, by arguing a client’s actions were due to brain abnormalities and thus out of his or her control. Or, a prosecutor could potentially use the paper to argue that MRI findings should be admissible as evidence that a defendant has committed a homicide, says Vogel, who has served as a consultant for court cases in California and Nevada, and helped investigate the brain of the Route 91 Harvest music festival shooter in 2017. “But then you’re [also] going to find an expert that will tear that [testimony] to pieces.”

Kiehl notes that his MRI study could also someday contribute to new evidence-based measures of homicidal risk. These measures could supplement current measures of violent behavior, such as psychological questionnaires, if future studies demonstrated they carried predictive weight, he says. Beyond courts of law, he also suggests that understanding how violent behavior arises could pave the way to better psychological treatment aimed at both rehabilitation and prevention.

https://www.the-scientist.com/notebook/secrets-in-the-brains-of-people-who-have-committed-murder-66589


Francisco Lopera, a neurologist at the University of Antioquia in Medellin, Colombia, has been painstakingly collecting brains, birth and death records from one sprawling Colombian family to study Alzheimer’s.Credit…Federico Rios Escobar for The New York Times


A woman with lots of beta-amyloid buildup (red) in her brain remained cognitively healthy for decades.

by Kelly Servick

In 2016, a 73-year-old woman from Medellín, Colombia, flew to Boston so researchers could scan her brain, analyze her blood, and pore over her genome. She carried a genetic mutation that had caused many in her family to develop dementia in middle age. But for decades, she had avoided the disease. The researchers now report that another rare mutation—this one in the well-known Alzheimer’s disease risk gene APOE—may have protected her. They can’t prove this mutation alone staved off disease. But the study draws new attention to the possibility of preventing or treating Alzheimer’s by targeting APOE—an idea some researchers say has spent too long on the sidelines.

“This case is very special,” says Yadong Huang, a neuroscientist at the Gladstone Institutes in San Francisco, California, who was not involved with the research. “This may open up a very promising new avenue in both research and therapy.”

APOE, the strongest genetic risk factor for Alzheimer’s, has three common forms. A variant called APOE2 lowers risk of the disease. The most common variant, APOE3, doesn’t influence risk. APOE4 raises risk; roughly half of the people with the disease have at least one copy of this variant.

Researchers have long contemplated targeting APOE with therapies. A team at Cornell University will soon start a clinical trial that infuses the protective APOE2 gene into the cerebrospinal fluid of people with two copies of APOE4.

But mysteries about APOE have kept it from becoming a front-runner among drug targets. “It does so many things that it’s confusing,” says Eric Reiman, a neuroscientist at the Banner Alzheimer’s Institute in Phoenix and a co-author on the new paper. The APOE protein binds and transports fats and is abundant in the brain. And the APOE4 variant seems to encourage the formation of sticky plaques of the protein beta-amyloid, which clog the brain in Alzheimer’s. But powerful amyloid-busting drugs have repeatedly failed to benefit patients in clinical trials. Some researchers saw no reason to try an APOE-targeting therapy that seemed to be “just a poor man’s antiamyloid treatment,” Reiman says.

The Colombian woman’s case suggests other ways APOE could affect Alzheimer’s risk. The woman participated in a study led by researchers at the University of Antioquia in Medellín that has tracked roughly 6000 members of her extended family. About one-fifth of them carried an Alzheimer’s-causing mutation in a gene called presenilin 1; these carriers generally developed dementia in their late 40s. Yet the woman didn’t show the first signs of the disease until her 70s, even though she, too, carried the mutation. “She’s definitely an outlier,” says cell biologist Joseph Arboleda-Velasquez of Harvard Medical school in Boston. (The research team is keeping the woman’s name confidential to protect her privacy.)

In Boston, a positron emission tomography scan of the woman’s brain revealed more amyloid buildup than in any other family member who has been scanned. “It was very striking,” says Yakeel Quiroz, a clinical neuropsychologist at Massachusetts General Hospital and Harvard Medical School. But the team found no signs of major damage to neurons, and minimal buildup of another Alzheimer’s hallmark: the misfolded protein tau. Whatever protection this woman had didn’t depend on keeping the brain amyloid-free. Instead, her case supports the idea that tau has a “critical role … in the clinical manifestations of Alzheimer’s disease,” says Jennifer Yokoyama, a neurogeneticist at the University of California, San Francisco.

Genome sequencing revealed two copies of a rare mutation in the APOE gene, the researchers report this week in Nature Medicine. First discovered in 1987, the mutation, known as Christchurch, occurs in a region separate from those that determine a person’s APOE2, 3, or 4 status. (The woman has the neutral APOE3 variant.) Previous research found that the Christchurch mutation—like the more common protective APOE2 mutation—impairs APOE’s ability to bind to and clear away fats and sometimes leads to cardiovascular disease.

The researchers also found that the mutation prevents APOE from binding strongly to other molecules called heparan sulfate proteoglycans (HSPGs), which coat neurons and other cells “like a carpet,” says Guojun Bu, a neuroscientist at the Mayo Clinic in Jacksonville, Florida, who has studied the interaction between these molecules and APOE.

APOE2 may also impair the protein’s ability to bind HSPGs. But how that could protect against disease isn’t clear. One possible clue: Research by neuroscientist Marc Diamond of the University of Texas Southwestern Medical Center in Dallas and his colleagues suggest the toxic tau protein relies on HSPGs to help it spread between cells. Maybe the less APOE binds to HSPGs, the harder it is for tau to spread.

But, Diamond cautions, “It will require much more study to understand if this relationship exists.” The Christchurch mutation might have protective effects unrelated to HSPGs; it’s also possible that mutations other than Christchurch protected the woman.

If hampering APOE’s normal binding really staved off her Alzheimer’s, future treatments might aim to mimic that effect. An antibody or small molecule could latch onto the APOE protein to interfere with binding, gene editing could change the structure of APOE to imitate the Christchurch variant, or a “gene silencing” approach could reduce production of APOE altogether.

Reiman hopes the new study will rally researchers to pursue treatments related to APOE. He, Quiroz, Arboleda-Velasquez, and other collaborators also posted a preprint on the medRxiv server on 2 November showing that people with two copies of APOE2 have lower Alzheimer’s risk than previously thought—about 99% lower than people with two copies of APOE4. “When it comes to finding a treatment that could have a profound impact on the disease,” Reiman says, “APOE may be among the lowest hanging fruit.”

https://science.sciencemag.org/content/366/6466/674

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