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Aging, Neuroscience, Stanford News, Stroke, Videos

Stanford expert responds to questions about brain repair and the future of neuroscience

Stanford expert responds to questions about brain repair and the future of neuroscience

One cool thing about being at Stanford is access to really, really smart people. Case in point, I get to work with William Newsome, PhD, who, in addition to doing really interesting neuroscience research, co-leads the group that made recommendations to the national BRAIN Initiative, and also directs the new Stanford Neurosciences Institute. He has a lot of insight into the state of neuroscience, where the field is headed, and what challenges scientists face in trying to better understand the brain and develop new therapies.

Newsome recently participated in an Open Office Hours, in which Stanford faculty take questions through Facebook, essentially opening their office doors to anyone with questions. He later recorded answers to those questions in the video above.

In addition to the full- length video, we’ve been posting short excerpts on Facebook. In this clip, Newsome discusses the dynamic nature of our brain’s connections. As he explains, the brain can switch connectivity to let us have one set of behaviors with our boss and another with our spouse.

In today’s installment, Newsome discusses efforts to repair nerves that are damaged in stroke, spinal cord injuries, traumatic brain injuries or other conditions. Stroke is of particular interest right now – the Neurosciences Institute that Newsome leads recently announced the creation of an interdisciplinary consortium at Stanford focused on stroke as one of their Big Ideas in Neuroscience.

In that segment, Newsome points out that nerves of our arms or legs, the so-called peripheral nervous system, can regrow if they get damaged. If you cut your finger, the nerves regrow. If you have a stroke or damage your spinal cord, the nerves don’t regrow. Newsome said:

What’s the difference between the central nervous system and the peripheral nervous system such that the central nervous system does not regrow most of the time yet the peripheral nervous system does? … When we get that knowledge the hope is that we’ll be able to set the conditions right for regrowth when there’s an injury and we’ll actually be able to help people recover function.

Previously: Deciphering “three pounds of goo” with Stanford neurobiologist Bill Newsome, Open Office Hours: Stanford neurobiologist taking your questions on brain research, Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more, Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute and Brain’s gain: Stanford neuroscientist discusses two major new initiatives

Aging, Health and Fitness, History, Neuroscience

Walking and aging: A historical perspective

Walk on by_flickrThe evidence that exercise helps stave off mental decline in elderly people has been mounting for several years now, but an article by Wayne Curtis in The Atlantic today puts this research in perspective by looking back a century at Edward Payson Weston’s walk from San Francisco to New York in 1909, when Weston was 70.

Curtis notes that the field of gerontology, the study of aging, had been around for less than a decade at that point. Most scientists thought brain cells were not capable of regenerating – something we know today that they’re most definitely capable of – and doctors were of the mind that too-vigorous exercise could harm mental acuity. Popular reaction to Weston’s trek is documented through newspaper accounts of the day:

A column in the Dallas Morning News admitted that many considered Weston’s walk from ocean to ocean “foolishness” and “an idle waste of time.” But, the writer asked, was it “preferred to the needless senility into which far too many men begin to drift at the period of three score years and 10?”

Curtis eventually moves into recent decades and details some of the recent research into how moderate to vigorous walking can actually improve mental acuity in several populations, including Alzheimer’s patients:

The results [of one long-term study], published in the journal Neurology, were sweeping and conclusive: Those who walked the most cut in half their risk of developing memory problems. The optimal exercise for cognitive health benefits, the 
researchers concluded, was to walk six to nine miles each week. That’s a mile to a mile and a half a day, without walking on Sundays if you’re inclined to follow Weston’s example of resting on the Sabbath. (This study concluded that walking an additional mile didn’t help all that much.)

I have to admit I’m glad I live in this century and not in Weston’s time. I don’t think I have the fortitude he showed in bucking popular opinion – or, to be honest, in walking.

Previously: Even old brains can stay healthy, says Stanford neurologistExercise and your brain: Stanford research highlighted on NIH Director’s blog and The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius
Photo by  Stefano Corso

Aging, Neuroscience, Research, Stanford News, Stroke

Drug helps old brains learn new tricks, and heal

Drug helps old brains learn new tricks, and heal

shatz_news

Our brains go through remarkably flexible periods in childhood when they can form new connections in a flash and retain information at a rate that leaves adults (or at least me) both impressed and also deeply jealous.

Now neurobiologist Carla Shatz, PhD, has developed a drug that at least in mice can briefly open that window for making new connections in the adult brain. It works as a sort of decoy, tricking other molecules in the cell into binding to it rather than to the “real” protein on the neuron’s surface. Without the bound molecules, the protein on the neuron’s surface releases its brake on synapse formation.

There are still a number of hurdles to overcome before the drug could work in people. The human version of the protein she studied is slightly different than the mouse version, and she had to inject the drug directly into the mouse brain. She would need to find a way of delivering the drug as a pill before it could be useful in people.

Despite those hurdles, the possibilities are exciting. From a story I wrote on the possible uses for such a drug, which she had tested in a form of blindness in mice:

This model that the team studied in mice directly applies to forms of blindness in people. Children who are born with cataracts need to have the problem repaired while the vision processing region of the brain is still able to form new connections with the eyes. “If the damage isn’t repaired early enough then it’s extremely difficult if not impossible to recover vision,” Shatz said.

If a version of the decoy protein could work in people, then kids born with cataracts in countries with limited access to surgery could potentially have their cataracts removed later, receive a drug, and be able to see. Similarly, the window could be briefly opened to help people recover from stroke or other conditions.

Previously: How villainous substance starts wrecking synapses long before clumping into Alzheimer’s plaques, “Pruning synapses” and other strides in Alzheimer’s research
Image, which shows neurons of the visual system in mice that have formed new connections, courtesy of the Shatz lab

Aging, Health Policy, In the News, Neuroscience, Patient Care

The toll of Alzheimer’s on caretakers

The toll of Alzheimer’s on caretakers

Loving Hands Vannesa Pike-Russell FlickrMy last grandparent, my paternal grandmother, passed away earlier this year. She lived into her 90s and, like both my maternal grandmother and grandfather, she suffered mild to moderate dementia in the final years of her life. My mother cared for each of them as one by one their health declined. She had ample support from our extended family, but she was the one who had to bathe them and help them go to the bathroom or remind repeatedly them that so-and-so relative had died many years ago. My parents’ experience taking care of elderly family members who no longer had their full mental faculties lasted two to three years in each case, unlike people who care for family members with Alzheimer’s disease – a task that can last a decade or more.

Last week, Tiffany Stanley wrote a feature in the National Review about her experience caring for her ailing aunt, Jackie, who was diagnosed with early onset Alzheimer’s. Stanley’s father had been caring for his sister when his congestive heart failure made him too ill to continue, so his 29-year-old daughter stepped in. She was unprepared for the realities of caring for an Alzheimer’s patient, and she chronicles her experiences with touching anecdotes about her family’s experiences, as well as a detailed look at Alzheimer’s care in the U.S. She also details the impact the disease has on caregivers:

Alzheimer’s places a heavy toll on family caregivers. Their own health suffers. Dementia caregivers report higher rates of depression and stress than the general population. Some studies show they have an increased risk for heart disease and stroke as well as higher mortality rates. Their own use of medical services, including emergency-room visits and doctors’ appointments, goes up, and their yearly health care costs increase by nearly $5,000, according to research from the University of Pittsburgh and the National Alliance for Caregiving. “Caring for a person with dementia is particularly challenging, causing more severe negative health effects than other types of caregiving,” reads an article in the American Journal of Nursing.

Stanley also writes about the tension between funding a cure – to keep people from spiraling late stage dementia – and caring for those who are already sliding down that route:

Lost too often in the discussion about a cure has been a much more basic, more immediate, and in many ways more important question: How can we better care for those who suffer from the disease? Dementia comes with staggering economic consequences, but it’s not the drugs or medical interventions that have the biggest price tag; it’s the care that dementia patients need. Last year, a landmark Rand study identified dementia as the most expensive American ailment. The study estimated that dementia care purchased in the marketplace—including nursing-home stays and Medicare expenditures—cost $109 billion in 2010, more than was spent on heart disease or cancer. “It’s so costly because of the intensity of care that a demented person requires,” Michael Hurd, who led the study, told me. Society spends up to $56,000 for each dementia case annually, and the price of dementia care nationwide increases to $215 billion per year when the value of informal care from relatives and volunteers is included.

The story is equal parts frustrating and heart-wrenching, but I came away much better informed about what a diagnosis entails, not just for the patients, but the families connected to them.

Previously: No one wants to talk about dying, but we all need to, Mindfulness training may ease depression and improve sleep for both caregivers and patients, Can Alzheimer’s damage to the brain be repaired?The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius and Exploring the psychological trauma facing some caregivers
Photo by Henry Rabinowitz

Aging, Biomed Bites, Neuroscience, Research, Videos

Even old brains can stay healthy, says Stanford neurologist

Even old brains can stay healthy, says Stanford neurologist

This is the fourth installment of our Biomed Bites series, a weekly feature that highlights some of Stanford’s most compelling research and introduces readers to innovative scientists from a variety of disciplines. 

Aged brains aren’t quite as agile as they once were — just take it from my nearly 91-year-old grandmother, who misplaces most everything, then spends hours hunting for things, giggling all the while.

She’s fortunate. Her memory loss is minor and met with humor. But memory loss, and its accompanying symptoms, devastate millions of families annually who watch their loved ones slip away. That’s why I’m rooting for Stanford neurologist Victor Henderson, MD. Henderson and his team works to decipher the neural changes that underlie both normal aging and what he calls “dementing disorders” such as Alzheimer’s disease.

Here’s Henderson, in the video above: “Our research is focused on risk factor identification related to cognitive aging and disorders like Alzheimer’s disease and devising intervention based on the risk factors we’ve identified.”

Turns out exposure to both synthetic and natural hormones such as estrogen can affect the brain, as can exercise. And here’s the part I like best:

The findings that we’ve had and the findings we hope to make in the future have important implications for ways that people might reduce the risk of developing dementing disorders and might be able to maintain cognitive health until late old age.

Here’s hoping that Henderson hits a homer.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Previously: Discover the rhythms of life with a Stanford biologistStudying the drivers of metastasis to combat cancer and Studying the link between post-menopausual hormones, cognition and mood

Aging, In the News, Neuroscience, Stanford News

Exercise and your brain: Stanford research highlighted on NIH Director’s blog

Exercise and your brain: Stanford research highlighted on NIH Director’s blog

B0007367 Thigh muscle fibrilsThomas Rando, MD, PhD, who studies stem cells in muscle and longevity, and Tony Wyss-Coray, PhD, who studies the immune system’s impact on the brain, were awarded an NIH Director’s Transformative Research Award to study the slew of molecules that muscles release and how they help muscle cells communicate with other cells. (Rando and Wyss-Coray call this cellular communication network “the communicome.”) The onset of both depression and Alzheimer’s disease have been shown to be delayed with exercise, and Rando and Wyss-Coray theorize that molecules released by muscles during exercise may be the key to understanding how exercise can affect brain function so profoundly and so beneficially.

Today on the NIH Director’s blog, Francis Collins, MD, highlighted the Stanford duo’s research:

To study the communicome, Wyss-Coray and Rando will use a technique called parabiosis to couple the circulatory systems of physically active mice with mice that are less active. If the “couch potato” mice benefit from the blood of the active mice, then the team will analyze the blood to find the responsible factor(s).

This is definitely high-risk high-reward research. It won’t be easy, but finding molecules that mimic exercise’s brain-boosting effects may open the door to new ways of preventing or treating age-related cognitive declines and a wide range of other neurological conditions. This is especially important for people for whom it is difficult or even hazardous to exercise because of conditions such as arthritis, osteoporosis, and Alzheimer’s disease and other forms of dementia.

Earlier this year, Wyss-Coray published a study showing that older mice that received transfusions of younger mice’s blood improved their brain function. That study was based in part on Rando’s previous research showing that young mouse blood could activate old stem cells and rejuvenate older tissue. Their new collaboration may shed more light on the molecular mechanisms behind such observations.

Previously: Young mouse to old mouse: “It’s all in the blood, baby”, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, “Alert” stem cells speed damage response, say Stanford researchers and Red light, green light: Simultaneous stop and go signals on stem cells’ genes may enable fast activation, provide “aging clock”
Photo, of thigh muscle fibrils, by David Gregory & Debbie Marshall, via Wellcome Images

Aging, Health and Fitness, Public Health, Research

Twenty-four percent of middle-aged and older Americans meet muscle-strengthening guidelines

Twenty-four percent of middle-aged and older Americans meet muscle-strengthening guidelines

free_weightsPast research has shown that strength training can benefit older adults’ health in numerous ways including arthritis relief, alleviating back pain, increasing bone density, improving sleep and boosting mental health. But despite these findings, a new study from Centers for Disease Control and Prevention (CDC) has found that few U.S. adults age 45 and older adhere to the Department of Health and Human Services’ muscle-strengthening recommendations.

The guidelines advise middle-aged and older adults to do moderate or high intensity muscle-strengthening activities that involve all major muscle group two or more days a week. Training can involve hand weights or weight machines, basic exercises such as sit-ups and push-ups or yoga and similar fitness practices.

In the latest study, researchers examined data from a telephone health survey conducted in 2011 by the CDC known as the U.S. Behavioral Risk Factor Surveillance System. For the survey, respondents provided information about the types of physical activities they engage in and frequency, as well as answered questions about if they specifically did exercises to strengthen their muscles. HealthDay reports:

Of all those who answered the questions on muscle strengthening, about 24 percent said they met the government’s recommendations.

Among those less likely than others to meet these guidelines were women, widows, those age 85 or older, people who were obese, and Hispanics. Participants who didn’t graduate from high school were also less likely to meet U.S. strength-training recommendations.

Jesse Vezina, of Arizona State University, and his fellow researchers concluded that interventions designed to encourage people to participate in strength training should target these high-risk groups.

Previously: Moderate exercise program for older adults reduces mobility disability, study shows, Help from a virtual friend goes a long way in boosting older adults’ physical activity and Do muscles retain memory of their former fitness?
Photo by Positively Fit

Aging, Health Policy, In the News, Medicine and Society

No one wants to talk about dying, but we all need to

No one wants to talk about dying, but we all need to

“Dying in America is harder than it has to be.”

That’s the headline of one of the stories published following the release of the Institute of Medicine’s 500-page report titled “Dying in America.” The report tackles head-on the difficult topic of how to provide individualized, appropriate care for patients with advanced serious illness in a country that is grappling with out-of-control health care costs.

Patients should, and can, take control of the quality of their life through their entire life, choosing how they live and how they die

Its conclusion: The system needs a major overhaul.

“Our current system is broken,” said David M. Walker, co-chair of the 21-member committee that authored the report and former U.S. Comptroller General from Bridgeport, Conn. “It does not result in the type of quality of care that people deserve and desire and it’s much more costly. Systematic changes are needed for more compassionate, affordable care.”

No easy solutions exist, the authors said at an hour-long press conference announcing the release of the report yesterday. Instead, they plan to spend the next year getting their message out to the public with far ranging goals for change: from more comprehensive coverage of palliative care by medical insurance, to more hours of palliative care education in medical and nursing schools, to improved communication between health care providers and their patients about their end-of-life care choices – along with a payer-system that reimburses for those conversations.

It’s a controversial topic that broke out into the public debate five years ago during the passage of the Affordable Care Act, when opponents of the bill claimed that a proposal for Medicare to reimburse doctors for counseling patients about living wills and advance directives would lead to bureaucrats setting up “death panels” to determine who deserved care.

But it’s also a topic that can no longer be ignored, authors of the report said. Too many Americans are suffering unnecessarily and as the elderly population continues to grow with the aging of the baby boom generation, these problems will continue to multiply.

“For most people, death does not come suddenly,” said Philip Pizzo, MD, co-author of the report and former dean of Stanford’s medical school, in an email to me discussing the conclusions of the report. “Instead, dying is a result of one or more diseases that must be managed carefully and compassionately over weeks, months, or even years, through many ups and downs.”

Physicians and other health care professionals can provide well-rounded care at the end of life to relieve patient pain, maximize functioning, alleviating emotional stress, and ease the burden of loved ones – all in a manner that is consistent with individual choices, he said.

“Patients should, and can, take control of the quality of their life through their entire life, choosing how they live and how they die,” Pizzo said.

But it’s not happening today.

“Studies show that doctors want to die in comfort at home at the end of life, but subject patients to high-intensity ineffective treatments,” he said. “Why?”

Previously: Study: Doctors would choose less aggressive end-of-life care for themselves, Former School of Medicine dean named to expert panel to reform end-of-life care in America, Communicating with terminally ill patients: A physician’s perspective and On a mission to transform end-of-life care

Aging, Complementary Medicine, Health and Fitness, Mental Health, Neuroscience, Research

Mindfulness training may ease depression and improve sleep for both caregivers and patients

Mindfulness training may ease depression and improve sleep for both caregivers and patients

meditatingDepression and poor sleep often affect both dementia patients and their caregivers. Now new research shows that caregivers and patients who undergo mindfulness training together experience an improvement in mood, sleep and overall quality of life.

While past studies have shown that yoga and simple meditations can relieve caregivers’ stress, researchers at Northwestern University wanted to determine if patients and caregivers could be trained together.

In the small study (subscription required), pairs of patients and caregiver participated in an eight-week mindfulness program. Patients were diagnosed with dementia due to Alzheimer’s disease or mild cognitive impairment, often a precursor to dementia. Caregivers included spouses, adult children or other relatives. The training was designed specifically to meet the needs of  individuals with memory loss due to terminal neurodegenerative illness and their caregivers. Researchers evaluated participants within two weeks of starting the program and two weeks of completing it.  Lead author Ken Paller, PhD, explained the results in a release:

We saw lower depression scores and improved ratings on sleep quality and quality of life for both groups… After eight sessions of this training we observed a positive difference in their lives.

Mindfulness involves attentive awareness with acceptance for events in the present moment… You don’t have to be drawn into wishing things were different. Mindfulness training in this way takes advantage of people’s abilities rather than focusing on their difficulties

Since caregivers often have limited personal time, mindfulness programs that accommodate them as well as patients could be an effective approach to helping both groups regularly attend sessions, said researchers.

The findings were published Monday in the American Journal of Alzheimer’s Disease and Other Dementias.

Previously: Regularly practicing hatha yoga may improve brain function for older adults, Study suggests yoga may help caregivers of dementia patients manage stress and How mindfulness-based therapies can improve attention and health
Photo by Alex

Aging, Autoimmune Disease, Immunology, Infectious Disease, Research, Stanford News

Our aging immune systems are still in business, but increasingly thrown out of balance

Our aging immune systems are still in business, but increasingly thrown out of balance

business as usual

Stanford immunologist Jorg Goronzy, MD, told me a few years ago that a person’s immune response declines slowly but surely starting at around age 40. “While 90 percent of young adults respond to most vaccines, after age 60 that response rate is down to around 40-45 percent,” he said. “With some vaccines, it’s as low as 20 percent.”

A shaky vaccine response isn’t the only immune-system slip-up. With advancing age, we grow increasingly vulnerable to infection (whether or not we’ve been vaccinated), autoimmune disease (an immune attack on our own tissues) and cancer (when a once well-behaved cell metamorphoses into a ceaselessly dividing one).

A new study led by Goronzy and published in Proceedings of the National Academy of Sciences, suggests why that may come about. The culprit he and his colleagues have fingered turns out not to be the most likely suspect: the thymus.

This all-important organ’s job is to nurture an army of specialized  immune cells called T cells. (The “T” is for “Thymus.”) T cells are capable of recognizing and mounting an immune response to an unbelievably large number of different molecular shapes, including ones found only on invading pathogens or on our own cells when they morph into incipient tumor cells.

Exactly which feature a given T cell recognizes depends on the structure of a receptor molecule carried in abundance on that T cell’s surface.  Although each T cell sports just one receptor type, in the aggregate the number of different shapes T-cells recognize is gigantic, due to a high rate of reshuffling and mutation in the genes dictating their receptors’ makeup. (Stanford immunologist Mark Davis, PhD, perhaps more than any other single individual,  figured out in the early 1980s how this all works.)

T cells don’t live forever, and their generation from scratch completely depends on the thymus. Yet by our early teens the organ,  situated  in front of the lungs at the midpoint of our chest, starts shriveling up and replaced by (sigh – you knew this was coming)  fat tissue.

After the thymus melts away,  new T-cells come into being only when already-existing ones undergo cell division, for example to compensate for the attrition of their neighbors in one or another immune-system dormitory (such as bone marrow, spleen or a lymph node).

It’s been thought that the immune-system’s capacity to recognize and mount a response to pathogens (or incipient tumors) fades away because with age-related T-cell loss comes a corresponding erosion of diversity:  We just run out of T-cells with the appropriate receptors.

The new study found otherwise.  “Our study shows that the diversity of the human T-cell receptor repertoire is much higher than previously assumed, somewhere in the range of one billion different receptor types,” Goronzy says. “Any age-associated loss in diversity is trivial.” But the study also showed an increasing imbalance, with some subgroups of T cells (characterized by genetically identical  receptors)  hogging the show and other subgroups becoming vanishingly scarce.

The good news is that the players in an immune response are all still there, even in old age. How to restore that lost balance is the question.

Previously: How to amp up an aging immune response, Age-related drop in immune responsiveness may be reversible and Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before
Photo by Lars Plougmann

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