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Aging, Genetics, Neuroscience, Podcasts, Research, Stanford News

The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius

The state of Alzheimer's research: A conversation with Stanford neurologist Michael Greicius

My colleague Bruce Goldman recently wrote an expansive blog entry and article based on research by Mike Greicius, MD, about how the ApoE4 variant doubles the risk of Alzheimer’s for women. I followed up Goldman’s pieces in a podcast with Greicius, who’s the medical director of the Stanford Center for Memory Disorders.

I began the conversation by asking about the state of research for Alzheimer’s: essentially, what do we know? As an aging baby boomer, I’m interested in the differences between normal, age-related cognitive decline versus cognitive declines that signal an emerging disease. Greicius said people tend to begin losing cognitive skills around middle age:

Every cognitive domain we can measure starts to decline around 40. Semantic knowledge – knowledge about the world – tends to stay pretty stable and even goes up a bit. Everything else… working memory, short term memory all tends to go down on this linear decline. The difference with something like Alzheimer’s is that the decline isn’t linear. It’s like you fall off a cliff.

Greicius’ most recent research looks at the certain increased Alzheimer’s risk ApoE4 confers on women. As described by Goldman:

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

In addition to the increased risk of Alzheimer’s for women with the ApoE4 variant, I asked Greicius how he advises patients coming into the clinic who ask about staving off memory loss. At this point, he concedes, effective traditional medication isn’t really at hand. “Far and away our strongest recommendations bear on things like lifestyle and particularly exercise,” he said. “We know, in this case from good animal models, that physical exercise, particularly aerobic exercise, helps brain cells do better and can stave-off various insults.” So remember, a heart smart diet along with aerobic exercise.

One last question for Greicius: What about those cognitive-memory games marketed to the elderly and touted as salves for memory loss – do they have any benefit? He’s riled now: “I get asked that all the time, and smoke starts coming out of my ears.” He says the games are nothing more than snake oil.  His advice when he gets asked the question: “Give that money to the Alzheimer’s Association or save it and get down on the floor with your grandkids and build Legos. That’s also a great cognitive exercise and more emotionally rewarding.”

Previously: Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s and Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor

Genetics, Podcasts, Stanford News

Whole genome sequencing: The known knowns and the unknown unknowns

Whole genome sequencing: The known knowns and the unknown unknowns

A few years ago, when I spoke with Euan Ashley, MD, associate professor of medicine and of genetics, about the promise of genomics for diagnosing and treating diseases he agreed that the field was in the wild, wild west. Now, in my latest 1:2:1 podcast with him, I asked how would he describe this moment in time, when so much has changed so quickly in whole genome sequencing (WGS). First, he said, the costs of sequencing the genome have plummeted. “At the point we spoke we were just coming off the $20,000 genome,” he told me. “Which seems remarkable, because we’d just been at… $200,000, and before that at the $2 million genome. In looking around in science… in medicine, I have not seen a technology that has changed that much.”

Euan AshleyAshley recently published a paper that my colleague, Krista Conger, has written about; in it, Ashley and his fellow researchers, Michael Snyder, PhD, professor and chair of genetics, and Thomas Quertermous, MD, professor of medicine, analyzed the whole genomes of 12 healthy people and took note of the degree of sequencing accuracy necessary to make clinical decisions in individuals, the time it took to manually analyze each person’s results and the projected costs of recommended follow-up. Quite clearly, Ashley says, the study shows “there are still some challenges, not that these are non-solvable problems.”

Ashley often cites an infamous quote that Donald Rumsfeld, former Secretary of Defense, said when he was asked about the lack of evidence of Iraqi weapons of mass destruction, as he thinks the questions that Rumsfeld raised about WMDs are analogous to the field of genetics today. Ashley told me:

There are really a number of things that we really know that we know, because they’re genetic variants we’ve seen many times. Also, there are a number of known unknowns… which are genes that we know are a problem but maybe variants we haven’t seen before, so they look pretty suspicious… There [are] the complete unknowns, the unknown unknowns… Many genes about which we really do not know very much at this point in time.

Who would have thought Rumsfeld was laying out the future of WGS and not just WMD’s?

Previously: Assessing the challenges and opportunities when bringing whole-genome sequencing to the bedside, Coming soon: A genome test that costs less than a new pair of shoes, Stanford researchers work to translate genetic discoveries into widespread personalized medicine, New recommendations for genetic disclosure released, Ask Stanford Med: Genetics chair answers your questions on genomics and personalized medicine and You say you want a revolution
Photo of Euan Ashley by Mark Tuschman

Addiction, FDA, Health Policy, Podcasts, Public Health

E-Cigarettes: The explosion of vaping is about to be regulated

E-Cigarettes: The explosion of vaping is about to be regulated

E-cigarettes are about to get zapped. To date, across the globe, they’ve been largely unregulated – and their growth since they first came on the scene in 2007 has been exponential. Now, in the first big regulatory action that is sure to spur similar responses across the pond, the European Parliament approved rules last week to ban e-cigarette advertising in the 28 EU member nations beginning in mid-2016.  The strong action also requires the products to carry graphic health warnings, be childproof and contain no more than 20 milligrams of nicotine per milliliter. It’s expected that the U.S. Food and Drug Administration will soon follow suit and the days of great independence for e-cigarettes will come to a crashing halt. A few U.S. cities, Los Angeles most recently, have banned e-cigarettes in public spaces.

e-cigUntil recently, I was completely ignorant about the whole phenomenon of e-cigarettes. What is the delivery system? Where are they manufactured? Are they a safe alternative to smoking? And how are they being marketed and to whom? Well here’s an eye opener: According to the Centers for Disease Control and Prevention, e-cigarette usage more than doubled among middle and high school students users from 2011 to 2012. Altogether, nearly 1.8 million middle and high school students nationwide use e-cigarettes.

Robert Jackler, MD, chair of otolaryngology at Stanford Medicine, has long studied the effects of tobacco advertising, marketing, and promotion through his center, SRITA (Stanford Research Into the Impact of Tobacco Advertising). After years of detailing how tobacco use became ubiquitous in the U.S. he’s now tracking the marketing of e-cigarettes, and what he’s found probably won’t surprise you. The same sales techniques that brought about the explosive growth of tobacco use are being deployed again to make e-cigarettes look sexy, cool and defiant.

While there are claims by the e-cigarette industry that e-cigarettes are important tools to help people kick the tobacco habit, there’s little evidence to date to back up that claim. And Jackler isn’t completely sold on the notion that e-cigarettes will bring about a great cessation of tobacco smoking; he sees them more as a continuity product. He told me:

What the industry would like to see you do is when you go to a place that you can’t smoke, that you pick up your e‑cigarette and you vape, and you get your nicotine dose in the airport when waiting, or when you’re in your workplace, or when you’re even in school, and that way, when you leave school or the workplace, you go back to the combustible tobacco products.

Sorry if I’m a bit cynical, but as an ex-smoker I find it hard to believe that Big Tobacco – which is increasingly getting into the e-cigarette business – doesn’t also see vaping as a way to continue to keep smokers smoking. Bubble gum flavors and packaging designed to resemble lipstick containers! Who’s really being targeted here?

After my 1:2:1 podcast (above) with Jackler, I’m convinced we’ve been down this road before and it wasn’t pretty health-wise. More than 16 million Americans suffer from a disease caused by smoking. Listen to the podcast and you be the  judge about the true intentions of those promoting e-cigarettes.

Previously: Stanford chair of otolaryngology discusses federal court’s ruling on graphic cigarette labelsWhat’s being done about the way tobacco companies market and manufacture products and Image of the Week: Vintage Christmas cigarette advertisement
Photo by lindsay-fox

Cardiovascular Medicine, Podcasts

Dick Cheney on his heart transplant: “It’s the gift of life itself”

Dick Cheney on his heart transplant: "It's the gift of life itself"

Cheney2Dick Cheney has lived with chronic heart disease for virtually all of his adult life. At 37, as a young man running for the U.S. Congress in Wyoming, he had his first heart attack. His last – a fifth – occurred in 2010 and by then having taken advantage of everything medicine and technology had to offer, Cheney knew he was at the end of the road. And, remarkably, as the former vice president told me in this 1:2:1 podcast, he didn’t fear death:

I concluded that sooner or later, I was going to run out of technology, run out of new innovations and developments in the area of heart medicine… I  thought about it, I guess, I was at peace. It was not painful. It wasn’t surprising or frightening. I had come to that point where I fully expected that I had lived a wonderful and remarkable life. I had a tremendous family. I had everything a man could ask for.

Facing end stage heart failure, in the summer of 2010 he received a left ventricular assist device commonly known as an LVAD. But he knew the device wouldn’t be enough. A transplant was the only option that would set aside decades of heart ailments and give him something he had thought was impossible: longevity. Twenty months later, at 71 years old, a late night phone call informed him a donor had been found. Life for Dick Cheney would begin anew.

Now, nearly two years after his transplant, Cheney and his cardiologist, Jonathan Reiner, MD, have written a book about his history of heart ailments, Heart: An American Medical Odyssey. As we were putting together the current issue of Stanford Medicine – a special on cardiology – it made sense to include an interview with Cheney, and so I pursued one.

Cheney launched the book last fall with a number of high-profile media interviews starting with Sanjay Gupta’s on CBS’ 60 Minutes. We spoke a few days before Thanksgiving when family matters were in the press. I decided not to repeat the buzz questions that had already consumed the press at the time – the Homeland scenario or whether his years of service in the White House afforded him special access to health care unavailable to everyone else. I pursued a different line.

This wasn’t the taciturn Cheney that I had feared as an interviewer. He was pensive, reflective and clearly extremely grateful that he was able to have this extension on life. His co-author Reiner told him that a heart transplant is a spiritual experience so I asked Cheney what’s been his? He told me:

It’s the gift of life itself… After you’ve been through all of the procedures and so forth and then anticipating death and finding your life has been extended that it’s miraculous… You have a sense that after you’ve been through all of  that, everything else is small. You don’t sweat the small stuff… A friend of mine asked me when I told him it was a spiritual experience: “Does that mean now, that you’re a Democrat?” I told him, “Well, not that spiritual.”

I closed the interview with a final question. What if he learned he had the heart of a liberal Democrat? Well, you’ll have to listen to the podcast or read the Q&A to find out his response.

Previously: Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions
Illustration, which originally appeared in Stanford Medicine magazine, by Tina Berning

Medicine and Literature, Mental Health, Podcasts

A conversation with Scott Stossel, author of My Age of Anxiety

A conversation with Scott Stossel, author of My Age of Anxiety

Stossel bookScott Stossel has written a tome on anxiety. The editor of The Atlantic magazine opens his best-selling memoir with a frightening yet comical scene at his wedding. He’s standing at the altar in a Vermont church, and his angst has ripped open his innards reducing him to a puddle of sweat and embarrassment. Anyone who’s suffered from severe anxiety can fully appreciate the yin and the yang of his moment:

The minister is droning on; I have no idea what he is saying… I am praying for him to hurry up so I can escape this torment… Seeing me – the sheen of flop sweat, the panic in my eyes – he is alarmed. “Are you okay?” he mouths silently. Helplessly, I nod that I am… As the minister resumes his sermon, here are three things I am actively fighting: the shaking of my limbs; the urge to vomit; and unconsciousness.

Anxiety disorders have a terrifying grip on nearly 44 million Americans. In the book, psychologist David Barlow, PhD, said of the affliction, “Anxiety kills relatively few people, but many more would welcome death as an alternative to the paralysis and suffering resulting from anxiety in its severe forms.”

I first came across Stossel’s work as a cover story in The Atlantic. Then, I discovered there was buzz about the book, as friends around the country were talking about it. For a few weeks, Stossel was everywhere – Fresh Air with Terry Gross, The Colbert Report, London’s Sunday Times, personal appearances around the U.S., and in laudatory book reviews in the nation’s top papers. I believed his exploration of  “fear, hope, dread, and the search for peace of mind” was something all anxiety sufferers seek, and I knew I wanted to snag him for a 1:2:1 podcast.

When we spoke, I thought I would open with a question I was very curious about. “You’re in the middle of a book tour,” I said to him. “It’s a New York Times best seller. You’re speaking in public. Flying around the county. Doing things that you really hate. So has the book been good for your anxiety, as your doctor posed it might be?”

Well, as you’ll hear, there have been ups and there have been downs. Unfortunately, there’s no Hollywood ending at this particular moment to his psychological puzzle. Yet Stossel does congratulate himself for finishing the book, a task at times he was doubtful he could or would achieve.

When I asked Stossel to read from the book, he said it was my choice what he read. So I chose a passage that was hopeful. It talks about how his anxiety, though often intolerable and miserable, could have an upside. “But it is also, maybe a gift – or at least the other side of a coin I ought to think twice about before trading in,” he writes.

In the end, I’m struck by the tremendous courage that it took for Stossel to lay himself bare – to expose some of his most idiosyncratic fears that have crippled him since childhood. He’s a brave man. It’s for that reason I think My Age of Anxiety has meaning well beyond the words on the page. It will help de-stigmatize this little dark corner of mental disorders. Through peeling back his own layers of psychic skin almost to the quick, I think he’ll change attitudes and  perceptions.

I especially liked what Elizabeth Gilbert, author of Eat, Pray, Love, said about the book:

It could not have been easy for Stossel to dissect his own anxiety so honestly in this memoir. But he was brave as hell to write it, and I’m glad he did, for he brings to this story depth, intelligence, and perspective that could enlighten untold fellow readers for years to come.

Amen!

Previously: Reframing reactions could reduce symptoms of social anxiety disorder, Stanford study shows and Does more authority translate into a reduction in stress and anxiety?
Image from Random House

Cancer, Podcasts, Stanford News

“How cancer becomes us”: A conversation with author and anthropologist Lochlann Jain

"How cancer becomes us": A conversation with author and anthropologist Lochlann Jain

Associate Professor of Anthropology S. Lochlann Jain's new book weaves her research with memoir and aims to start a new conversation about cancer as a cultural, not just medical, phenomenon.I asked Stanford anthropologist Lochlann Jain, PhD, author of “Malignant: How Cancer Become Us,” why, when there are thousands of books on the market about cancer, we needed another one. She agreed there are many. There are superb histories, interesting and excellent memoirs, and penetrating looks at the environmental causes of cancer out there, but, she said, “what we’re missing is an analysis of how cancer is such a large part of America’s political, social and economic life.”

When we first met over coffee to talk about the book, I asked Jain how she  would define cancer, having been a member of its club. “It complicated,” she replied. “I didn’t expect to write about cancer. I just thought I’d get this treatment over with and go back to my work. But then I realized, the whole experience was just so full of paradox, I couldn’t just let it go.”

And paradoxes she does write about: We fight it, yet we produce it. Science, medicine, economics and policy are often at odds with each other. As she told me:

Each of America’s iconic industries – agriculture, oil and gas, cosmetics, plastics, pesticides, tobacco, medicine, construction, military – has undoubtedly led to tens of millions of cancer deaths. The unique way in which cancer presents, decades after exposure, makes it central to the growth of both the industries and the illness, in short to the existence of the United States, as we know it.

She also talked to me about the blame and shame game that accompanies a diagnosis of cancer. She brings clarity to the issue of why victims of cancer are dropped into a torturous inner debate of shoulds and coulds and woulds.

I was completely riveted by our conversation. ”Malignant” is an extraordinarily original piece of writing that takes a microscopic lens to the complex and confounding world of cancer. I hope you’ll find my 1:2:1 podcast with her of value. In my mind, Jain adds a truly unique voice to the literature of cancer.

Previously: Stanford professor dispels “too young for cancer” myth
Photo by L.A. Cicero/Stanford News Service

Ethics, Patient Care, Podcasts

What happened inside New Orleans’ Memorial Hospital? A conversation with Pulitzer Prize-winning author Sheri Fink

What happened inside New Orleans' Memorial Hospital? A conversation with Pulitzer Prize-winning author Sheri Fink

Memorial Medical Center is seen Monday, Sept. 12, 2005, in New Orleans, after more than 40 bodies were recovered Sunday at the 317-bed hospital. Hospital assistant administrator David Goodson said patients died while waiting to be evacuated over the four days after the hurricane hit, as temperatures inside the hospital reached 106 degrees.  (AP Photo/Rick Bowmer)What happened at Memorial Hospital in New Orleans after Hurricane Katrina struck and paralyzed the city? Pulitzer Prize winner Sheri Fink details the hospital’s struggles for survival in her new book, Five Days at Memorial. It’s a harrowing tale of colossal failures within Memorial and also outside as the federal, state and local governments bungled their response. I find myself still outraged eight years later, wondering how a tragedy of this magnitude could happen to an American city.

In addition to the horror of a hospital in chaos due to a storm of historic proportions, the story of Memorial is filled with ethical conundrums about what constitutes humane health care. Did health care workers choose life for some patients and death for others? Three health care workers were arrested and faced criminal allegations that they deliberately injected a number of patients with drugs to hasten their deaths. In the end, a New Orleans grand jury declined to indict even though the State Attorney General maintained to the end that a number of the dead were victims of homicide.

In her finely detailed investigative work, Fink brings the reader into Memorial for a minute by minute harrowing recounting of what happens when things fall apart in a hospital. Five Days at Memorial is a stunning read, and I was pleased to be able to talk with Fink at length for my latest 1:2:1 podcast. As I wrote in an earlier blog entry:

Put yourself [in place of the health care workers]. What would you have done? Are the ethical lines clear to you? Is what happened inside Memorial black and white? Or is it gray?

Fink holds an MD and PhD from Stanford’s School of Medicine.

Previously: Pulitzer Prize-winner Sheri Fink: the final hours at New Orleans Memorial, New York Times wins three Pulitzers for health stories and Murky waters: A look at Memorial Medical Center after Hurricane Katrina
Photo by ASSOCIATED PRESS

Pediatrics, Podcasts, Public Health

A conversation with “Children’s Defender” Marian Wright Edelman

A conversation with "Children's Defender" Marian Wright Edelman

EdelmanMarian Wright Edelman is a force of nature. Ask her a question and she reels off facts and figures rapid roll. When we were considering which noted individual to feature in a Q&A for our current issue of Stanford Medicine, which focuses on pediatrics, she stood out. Edelman’s leadership on children’s issues is awe-inspiring. I’ve listened to my 1:2:1 podcast with her and read our conversation, “The Children’s Defender”, numerous times during the editing process of the magazine – and I’m still touched by her passion, dedication and commitment.

Children’s Defense Fund, which Edelman founded forty years ago, has been at the forefront of overhauling public policy in child poverty, early childhood development, education and health. They’ve also worked to prevent gun deaths among children and teens for more than two decades. During our talk, Edelman said she wished they would have closed their doors long ago and that the myriad of issues that confront children would have been solved. But the struggle continues. She carries forth that mission extremely well.

Previously: From womb to world: Stanford Medicine Magazine explores new work on having a baby
Photo courtesy of Children’s Defense Fund

Cancer, Podcasts, Women's Health

Red Sunshine: One doctor’s journey surviving stage 3 breast cancer

Red Sunshine: One doctor's journey surviving stage 3 breast cancer

Red Sunshine cover - smallThere’s something so raw and intimate about Kim Allison’s cancer memoir, Red Sunshine, that as a reader at times you feel like you might be invading her privacy. But as the Stanford cancer pathologist told me in our 1:2:1 conversation, she mulled over what if anything might be too personal to share and decided that if she was going to write a book about her battle with Stage 3 breast cancer she would do it with candor.

I was curious. How does a cancer pathologist who peers through a microscope every day to analyze biopsies of strangers look at her own malignant cells? What’s it like to have the dual role of patient and cancer doctor? And, how does a mother of two young children even contemplate the question of death?

In person, Allison is as disarming and comfortable talking about her cancer as she is detailing it in the book. Now, five years cancer-free, she can look back and call herself a survivor. Her kids, nine and six, still too young to fully comprehend their mother’s journey from desperation to renewal, see the history of her illness through the scars on her body. The cancer may be gone now, but for Allison it’s certainly not forgotten.

I’m sure that her story will give hope and perhaps even solace to other women (and men too) looking down at the beast of cancer. Red Sunshine is a tale about weathering a storm, surviving the dark times and in the end coming out whole.

Medical Education, Medicine and Literature, Podcasts, Stanford News

Starting a new career in academic medicine? Here’s a bible for the bedside: The Academic Medicine Handbook

Starting a new career in academic medicine? Here's a bible for the bedside: The Academic Medicine Handbook

Roberts_book_coverWhen I spoke with Laura Roberts, MD, chair of psychiatry at Stanford, for a 1:2:1 podcast about the new book she edited, The Academic Medicine Handbook, I told her I thought every profession needs what she’s created, a hands-on guide on how to achieve success. Think about it. How much of our professional success is determined by skills we were never taught in college or grad school? In Chapter One, she writes, “…my sense is that nearly all early-career faculty members experience, as I did, an unsettling combination of feeling overly schooled and yet, still unprepared. Decades of formal education, as it turns out, are insufficient for some of the unexpected and labor-intensive everyday duties of the instructor/assistant professor…”

So here it is, a soup-to-nuts manual that gives academics in medicine a road map for how to excel.  It covers the basics, with chapters on how to manage time, how to give a lecture and how to prepare the best curriculum vitae. And it gets even more sophisticated, with how to evaluate an offer letter, how to understand flaws in clinical research and how to prepare an IRB application. The bottom line: If you’re a young professional just beginning a career in academic medicine, here’s a bible to have along your bedside.

Stanford Medicine Resources: