A Jazz Drummer’s Fight to Keep His Own Heart Beating

Corey Kilgannon wrote . . . . . . . . .

In the 1960s, Milford Graves became a groundbreaking drummer in avant-garde jazz, but intertwined with his career had been his constant study of music’s impact on the human heart.

Now Mr. Graves, a 78-year-old who lives in Jamaica, Queens, has become his own subject: He has amyloid cardiomyopathy, sometimes called stiff heart syndrome.

Doctors have informed him that the condition, also called cardiac amyloidosis, has no cure. When he received the diagnosis in 2018, he was told he had six months to live.

Since then, Mr. Graves said, he has come close to death several times because of fluid filling his lungs. His legs too weakened to walk, he remains in a recliner in his living room with a tube feeding medicine to his heart and another draining fluid from his midsection.

But he has hardly surrendered to the illness. Although he is under the care of a cardiologist, he is also treating himself with the alternative techniques he has spent decades researching.

Since the 1970s, Mr. Graves has studied the heartbeat as a source of rhythm and has maintained that recording musicians’ most prevalent heart rhythms and pitches, and then incorporating those sounds into their playing, would help them produce more personal music.

He also believes that heart problems can be helped by recording a patient’s unhealthy heart and musically tweaking it into a healthier rhythm to use as biofeedback.

In recent months, Mr. Graves has been listening constantly to his own heart with a stethoscope and monitoring it with an ultrasound device he bought on eBay.

“It turns out, I was studying the heart to prepare for treating myself,” he said.

His diagnosis has only invigorated his research, musical explorations and creative output as a visual artist, said Mr. Graves, whose daily fight against the disease has become something of a performance art project.

He said he is rushing to further his research and organize it, so that it can be continued after his death by his students, who are fastidiously documenting and videotaping his daily activity, both for his archives and for an exhibition in September at the Institute of Contemporary Art in Philadelphia.

The show’s curator, Mark Christman, visits Mr. Graves and gathers his latest work, from sculptures to customized drums to new videos of Mr. Graves playing.

Mr. Graves has no idea how long he will live — “It could be three days, it could be a month,” or longer — but he is adamant that he will be strong enough to play live for the show, perhaps streamed from his recliner.

Where some might see cruel irony in being afflicted by heart disease, which he has studied for 45 years, he sees a challenge.

“It’s like some higher power saying, ‘OK, buddy, you wanted to study this, here you go,” he said. “Now the challenge is inside of me.”

He wonders if he has somehow “internalized” the subject of his study.

“I ask myself, ‘Why did I get something that, in my research, I’ve been trying to rectify?’” he said. “It’s a rare disease with very little research on it. The experts say there’s nothing to be done, so I have to look inward for answers.”

Mr. Graves has long said that a healthy heart beats with flexible, varying rhythms that respond to stimuli from the body. The rhythms, he said, bear similarities to some traditional Nigerian drumming styles, and he has fashioned some of his drumming approaches along these lines.

Because of the abnormal heartbeats caused by his disease, which stiffens the heart muscle and can lead to heart failure, what he hears now in his own heart is the “sound of survival,” he said.

It sounds less elastic and more plodding than before the diagnosis, he said, with a more metronomic regularity that he has called a rigid, unhealthy quality in a heartbeat.

He is practicing his biofeedback techniques by listening to his heart with a stethoscope and mimicking the rhythm and melody by singing and playing on a drum near his recliner. He also plays recordings of his own heart’s sounds on the drumhead with the help of electronic transducers, effectively turning the drumhead into a speaker.

That has helped him come up with drumming techniques, including adjustments in drumhead tensions and new stick styles. It’s still drum practice, but with higher stakes.

Mr. Graves has seen a resurgence in popularity in recent years, with exhibitions of his art and research, festival performances and an acclaimed full-length documentary, “Milford Graves Full Mantis.”

“Instead of going into despair, his response was, ‘I’ve been asked to look deeper at this,’” said Jake Meginsky, the film’s co-director and a longtime assistant of Mr. Graves. “He’s surviving this prognosis, and through his creative process he’s offering us a record on what that survival is like.”

Mr. Graves approach is no surprise to those familiar with his unconventional life path.

He grew up in the South Jamaica housing projects and in the 1960s played with such avant-garde musicians as Cecil Taylor and Albert Ayler, with whom he performed at John Coltrane’s funeral in 1967. He turned down offers from Miles Davis to join Davis’s band.

In more recent years, he has also collaborated with the rocker Lou Reed, the pianist Jason Moran and the avant-garde saxophonist John Zorn.

Mr. Graves became a largely self-taught musician and scientific researcher, delving into herbal medicine, holistic healing, acupuncture, martial arts and other disciplines.

With only a high school diploma and minimal formal medical training, he taught music healing and drumming classes at Bennington College in Vermont for nearly 40 years before retiring in 2012.

He developed a martial-arts style modeled after the movements of the praying mantis and dance traditions from West African styles and the Lindy Hop.

“He did pretty much everything on his own, and it’s very important that his work continue, so he wants to leave everything in the right places with the right people,” his wife, Lois, said. “He knows he has more work to do and he’s going to get it done.”

Since 1970, Mr. and Ms. Graves have lived in a home in Queens that he has decorated with a Gaudíesque mosaic of stones and colored glass. The Graveses have turned the yard into a lush garden, dense with citrus trees, herbs and exotic plants. He converted a free-standing garage into an ornate temple that was often used as a dojo for martial arts.

But it is the basement where his heart research was mainly conducted. The space is packed with African idols, anatomical models, herbal extracts, African drums and a hodgepodge of heart-monitoring equipment displaying intricate electrocardiogram readouts.

Here, he said, he has treated students, neighbors and colleagues, and since 1990 has recorded perhaps 5,000 heartbeats. Mr. Graves created programs to analyze the heart’s rhythms and pitches caused by muscle and valve movement. He found ways to amplify the more obscure patterns and complex melody lines in the vibration frequencies underneath the basic thump-THUMP heartbeat, and use them for both musical and medical analysis.

In 2000, he received a Guggenheim grant to purchase heart-monitoring equipment. And in 2017, he co-patented technology for using heart melodies to regenerate stem cells.

Dr. Baruch Krauss, who teaches pediatrics at Harvard Medical School and is an emergency physician at Boston Children’s Hospital, said Mr. Graves’s work “has a lot of potential and possibility” if it were to be furthered in a clinical setting.

“There’s a lot there to be studied and used as a basis for further research,” said Dr. Krauss, who follows Mr. Graves’s work.

“He’s continuously inquisitive and creative and interested,” he added, “and this condition really hasn’t slowed him down.”

In his living room on a recent Sunday, one of Mr. Graves’s students, Peyton Pleninger, 24, helped him set up a device to play heart sounds and assisted him with making an assemblage for the art show.

“I don’t want to leave the planet with things undone,” Mr. Graves said.

Source : The New York Times

Antibody Designed to Recognize Pathogens of Alzheimer’s Disease

Researchers have found a way to design an antibody that can identify the toxic particles that destroy healthy brain cells – a potential advance in the fight against Alzheimer’s disease.

Their method is able to recognise these toxic particles, known as amyloid-beta oligomers, which are the hallmark of the disease, leading to hope that new diagnostic methods can be developed for Alzheimer’s disease and other forms of dementia.

The team, from the University of Cambridge, University College London and Lund University, designed an antibody which is highly accurate at detecting toxic oligomers and quantifying their numbers. Their results are reported in the Proceedings of the National Academy of Sciences (PNAS).

“There is an urgent unmet need for quantitative methods to recognise oligomers – which play a major role in Alzheimer’s disease, but are too elusive for standard antibody discovery strategies,” said Professor Michele Vendruscolo from Cambridge’s Centre for Misfolding Diseases, who led the research. “Through our innovative design strategy, we have now discovered antibodies to recognise these toxic particles.”

Dementia is one of the leading causes of death in the UK and costs more than £26 billion each year, a figure which is expected to more than double in the next 25 years. Estimates put the current cost to the global economy at nearly £1 trillion per year.

Alzheimer’s disease, the most prevalent form of dementia, leads to the death of nerve cells and tissue loss throughout the brain, resulting in memory failure, personality changes and problems carrying out daily activities.

Abnormal clumps of proteins called oligomers have been identified by scientists as the most likely cause of dementia. Although proteins are normally responsible for important cell processes, according to the amyloid hypothesis, when people have Alzheimer’s disease these proteins -including specifically amyloid-beta proteins – become rogue and kill healthy nerve cells.

Proteins need to be closely regulated to function properly. When this quality control process fails, the proteins misfold, starting a chain reaction that leads to the death of brain cells. Misfolded proteins form abnormal clusters called plaques which build up between brain cells, stopping them from signalling properly. Dying brain cells also contain tangles, twisted strands of proteins that destroy a vital cell transport system, meaning nutrients and other essential supplies can no longer move through the cells.

There have been over 400 clinical trials for Alzheimer’s disease, but no drug that can modify the course of the disease has been approved. In the UK, dementia is the only condition in the top 10 causes of death without a treatment to prevent, stop, or slow its progression.

“While the amyloid hypothesis is a prevalent view, it has not been fully validated in part because amyloid-beta oligomers are so difficult to detect, so there are differing opinions on what causes Alzheimer’s disease,” said Vendruscolo. “The discovery of an antibody to accurately target oligomers is, therefore, an important step to monitor the progression of the disease, identify its cause, and eventually keep it under control.”

The lack of methods to detect oligomers has been a major obstacle in the progress of Alzheimer’s research. This has hampered the development of effective diagnostic and therapeutic interventions and led to uncertainty about the amyloid hypothesis.

“Oligomers are difficult to detect, isolate, and study,” said Dr Francesco Aprile, the study’s first author. “Our method allows the generation of antibody molecules able to target oligomers despite their heterogeneity, and we hope it could be a significant step towards new diagnostic approaches.”

The method is based on an approach for antibody discovery developed over the last ten years at the Centre for Misfolding Diseases. Based on the computational assembly of antibody-antigen assemblies, the method enables the design of antibodies for antigens that are highly challenging, such as those that live only for a very short time.

By using a rational design strategy that enables to target specific regions, or epitopes, of the oligomers, and a wide range of in vitro and in vivo experiments, the researchers have designed an antibody with at least three orders of magnitude greater affinity for the oligomers over other forms of amyloid-beta. This difference is the key feature that enables the antibody to specifically quantify oligomers in both in vitro and in vivo samples.

The team hopes that this tool will enable the discovery of better drug candidates and the design of better clinical trials for people affected by the debilitating disease. They also co-founded Wren Therapeutics, a spin-out biotechnology company based at the Chemistry of Health Incubator, in the recently opened Chemistry of Health building, whose mission it is to take the ideas developed at the University of Cambridge and translate them into finding new drugs to treat Alzheimer’s disease and other protein misfolding disorders.

The antibody has been patented by Cambridge Enterprise, the University’s commercialisation arm.

Source: EurekAlert!

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New Imaging Tool Helps Researchers See Extent of Alzheimer’s Early Damage

Bill Hathaway wrote . . . . . . . . .

New imaging technology allows scientists to see the widespread loss of brain synapses in early stages of Alzheimer’s disease, a finding that one day may help aid in drug development, according to a new Yale University study.

The research, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, compared the density of synapses, which transmit signals between neighboring brain cells, in people with early stages of Alzheimer’s with those of people who have no evidence of the disease. As expected, the loss of synapses in those with an early stage of Alzheimer’s was particularly high in areas surrounding the hippocampus, an area of the brain crucial to formation of memory, the scientists report.

“However, our new methods enable us to detect widespread synaptic losses thoughout the brain,” said Yale’s Adam Mecca, assistant professor of psychiatry and first author of the paper. “This gives us confidence that we may use these results as a biomarker outcome for therapeutic trials, which could help speed development of new drugs to combat the disease.”

To get a clearer picture of the early effects of Alzheimer’s, the researchers used positron emission tomography (PET) imaging of a protein found in almost all brain synapses. Previous imaging technologies had been able to show in broad strokes the loss of brain tissue or reduced brain metabolism in Alzheimer’s. However, the new PET scans show the distribution of synaptic damage, a more specific disease pathology present at early stages of the disease, the authors say.

“These methods will allow us to examine synaptic loss at still earlier stages of disease — when people have evidence of Alzheimer’s pathogenesis but have not yet manifested symptoms,” said Christopher van Dyck, professor of psychiatry, neurology, and neuroscience, and senior author of the study.

Source: Yale University

Researchers Find Our Brains are Powerful, but Secretive

Talor Kubota wrote . . . . . . . . .

When Stanford University neuroscientist Brian Knutson tracked his smartphone usage, he was shocked to learn that he spent twice as much time on his phone as he had anticipated.

Research investigating the neuroscience of choice have found that our brains hold hidden information about the viral potential of online videos. (Image credit: Getty Images)

“In many of our lives, every day, there is often a gap between what we actually do and what we intend to do,” said Knutson, who is a professor of psychology in the School of Humanities and Sciences, reflecting on his smartphone habits. “We want to understand how and why people’s choices lead to unintended consequences – like wasting money or even time – and also whether processes that generate individual choice can tell us something about choices made by large groups of people.”

Toward that end, Knutson and colleagues are investigating an approach he calls “neuroforecasting” – in which they use brain data from individuals who are in the process of making decisions to forecast how larger groups of unrelated people will respond to the same choices. His lab’s latest neuroforecasting work in collaboration with researchers at Stanford’s Graduate School of Business, published Mar. 9 in the journal Proceedings of the National Academy of Sciences, focused on how people spend time watching videos online.

By scanning people’s brains as they selected and watched videos, the researchers discovered that both neural and behavioral responses to a video could forecast how long other people will watch that same video on the internet. When forecasting video popularity on the internet, however, brain responses were the only measure that mattered.

“Here, we have a case where there is information contained in subjects’ brain activity that allows us to forecast the behavior of other, unrelated, people – but it’s not necessarily reflected in their self-reports or behavior,” explained Lester Tong, a graduate student in the Knutson lab. “One of the key takeaways here is that brain activity matters, and can even reveal hidden information.”

Cerebral secrets

The researchers analyzed data from 36 participants, who watched videos while being scanned with a brain imaging technique known as fMRI. The researchers also monitored participants’ behavior – like whether they chose to skip a video – and asked them questions about each video, like how it made them feel and whether they thought it would be popular. Then, they examined how those same videos performed on the internet in terms of daily views and average duration of viewings.

Because videos are complex and change over time, the researchers specifically examined brain responses to the start and end of videos, as well as average responses to each video. They focused on activity in brain regions previously shown to predict peoples’ willingness to spend money.

The researchers found that longer video views were associated with activity in reward-sensitive regions of the brain, while shorter video views were associated with activity in regions sensitive to arousal or punishment. The subjects’ answers to questions about the videos also predicted their own behavior.

When it came to forecasting the behavior of others online, however, the data told a different story. Both the group’s behavior and brain activity forecasted how long people would watch the videos online. However, only group brain activity forecasted the popularity (or views per day) of each video online. During just the first four seconds of watching each video, more activity in the brain region associated with anticipating reward forecasted a video’s popularity online, whereas heightened activity in the region associated with anticipating punishment forecasted decreased popularity.

“If we examine our subjects’ choices to watch the video or even their reported responses to the videos, they don’t tell us about the general response online. Only brain activity seems to forecast a video’s popularity on the internet,” explained Knutson, who co-leads the NeuroChoice Initiative of the Stanford Wu Tsai Neurosciences Institute.

This and related research indicate that some steps of the choice process may prove more useful for broad neuroforecasting than others. By teasing out the specifics of which steps matter, the researchers think neuroforecasting might even apply across groups of different ages, genders, races or cultures when they show similar early neural responses.

Valuable choices

These findings suggest similarities between neuroforecasting how people spend time and how they spend money online, which the team has previously studied in non-traditional markets, including online markets for micro-loans and crowdfunding.

Source: Stanford University

Surgery with Anesthesia not Associated with Indicator of Alzheimer’s Disease

Jay Furst wrote . . . . . . . . .

Older adults who have surgery with general anesthesia may experience a modest acceleration of cognitive decline, even years later. But there’s no evidence of a link to Alzheimer’s disease, according to new research from Mayo Clinic.

The research, published in the British Journal of Anaesthesia, examined brain scans from 585 patients, ages 70 to 91 ― 493 of whom had at least one surgery with general anesthesia. The analysis found cortical thinning in cerebral areas but no significant evidence of deposits of amyloid protein, a hallmark of Alzheimer’s disease. The cortex is the outermost layer of the brain’s nerve cell tissue, and thinning of that tissue is associated with diminished cognitive functions.

“This finding suggests that the modest cortical thinning is not related to Alzheimer’s disease pathology, but is caused by other processes,” says Juraj Sprung, M.D., Ph.D., a Mayo Clinic anesthesiologist and first author of the study. “These results are reassuring and consistent with the conclusion that surgery and anesthesia do not increase the risk for development of Alzheimer’s disease.”

The potential link between surgery with anesthesia and cognitive decline in older adults has been examined for many years, and concerns have grown as animal studies have indicated that exposure to inhaled anesthetics may be related to brain changes similar to those seen with Alzheimer’s disease.

Alzheimer’s disease is a progressive disorder that causes brain cells to degenerate and die. It is the most common cause of dementia and the sixth leading cause of death in the U.S. Also, Alzheimer’s disease causes a continuous decline in cognition and behavior that disrupts a person’s ability to function. While there is no cure, some medications can slow its progression. An estimated 5.8 million Americans are living with the disease, according to the Alzheimer’s Association.

One of the key indicators of Alzheimer’s disease is a buildup of proteins in the cortical area of the brain, which can be visualized by positron emission tomography (PET) scans. The protein deposits, called “amyloid plaques,” have a toxic effect on neurons and can precede any clinical symptoms of the disease by 30 years or more.

The Mayo Clinic study used data from the Mayo Clinic Study of Aging, which started in 2004 and has data on more than 5,000 participants ― all from Olmsted County, Minnesota, where Mayo Clinic in Rochester is located. The study analyzed 585 patients, 493 of whom had at least one surgery with general anesthesia after age 40, and later had PET scans. Of those, the median time between surgery and the PET scan was 25.9 years.

The researchers used two methods to define amyloid deposition in the PET scans. “Regardless of the definition used, no significant associations were detected between exposure to surgery and anesthesia, and increased amyloid deposition,” Dr. Sprung says.

Dr. Sprung and Mayo Clinic colleagues published a study last year that also noted the association between surgical anesthesia and cortical thinning in the signature region for Alzheimer’s disease. The study cautioned that the pathogenesis and mechanisms driving these changes required more study.

The new study concludes that the cortical thinning was not associated with pathologic changes related to Alzheimer’s, but was caused by other undetermined processes.

“Older adults who are considering surgery, and their families, must be properly informed of the risk for slightly accelerated cognitive decline in the years following surgery,” says Dr. Sprung. “However, they should also be made aware that this potential impact may be related to preexisting conditions that necessitate the surgery.”

“Most important, patients should be reassured by our findings that surgery with anesthesia does not lead to changes associated with Alzheimer’s disease,” says Dr. Sprung.

Source: Mayo Clinic

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