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Aging, Genetics, Men's Health, Neuroscience, Research, Stanford News, Women's Health

Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

brain cactus - smallSince the early 1990s, when Duke University neurologist Allen Roses, MD, first broke the news, it’s been known that a person carrying the gene variant known as ApoE4 is at elevated risk of getting Alzheimer’s disease. To this day ApoE4 is the strongest known single genetic risk factor for Alzheimer’s, a progressive neurological syndrome that robs its victims of their memory and reasoning ability.

But only now is it looking certain that the increased Alzheimer’s risk ApoE4 confers is largely restricted to women. Men’s fates don’t seem to be altered nearly as much by the genetic bad penny that is ApoE4, according to a new Annals of Neurology study led by Mike Greicius, MD, medical director of the Stanford Center for Memory Disorders.

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.

What the heck is ApoE4 for, anyway? In my release on the new study, I wrote:

The ApoE gene is a recipe for a protein important for shuttling fatty substances throughout the body. This is particularly important in the central nervous system, as brain function depends on rapid rearrangement of such fatty substances along and among nerve cell membranes. The ApoE gene comes in three varieties — ApoE2, ApoE3 and ApoE4 — depending on inherited variations in the gene’s sequence. As a result, the protein that the gene specifies also comes in three versions, whose structures and fatty-substance-shuttling performance differ. Most people carry two copies of the ApoE3 gene variant (one from each parent). But about one in five people carries at least one copy of ApoE4, and a small percentage have two ApoE4 copies. Numerous studies … have confirmed that ApoE4 is a key risk factor for Alzheimer’s disease, with a single copy of ApoE4 increasing that risk twofold or fourfold. Carrying two copies confers 10 times the risk of Alzheimer’s.

Early hints in the medical literature that the ApoE4 variant exerted differential effects on women’s versus men’s brains were largely ignored until now, says Greicius. He says that’s because most of the seminal ApoE4/Alzheimer’s genetics research was conducted as case-control studies: The ApoE4 gene version’s frequency in people with Alzheimer’s was compared to its frequency in people without the disease. (About half of those with Alzheimer’s, but only about 15 percent without it, are positive for ApoE4.)

But that method has limitations, says Greicius: “About 10-15 percent of ‘normal’ 70-year-olds will develop Alzheimer’s if you wait five or ten years.” Their lurking in the “normal” group dilutes the results. Moreover, Greicius says,“these kinds of genetic studies are looking for needles in a haystack, so they require large numbers of subjects – thousands – to achieve statistical significance. If you want to further examine male/female differences, you have to double the sample size.” That’s costly.

And that’s how come the large government- and industry-supported repositories to which Greicius and his team resorted are such a great idea.

Previously: Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s, Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor and A one-minute mind-reading machine? Brain-scan results distinguish mental states
Photo by Sean Michael Ragan

Cardiovascular Medicine, Genetics, Health and Fitness, Men's Health, Stanford News

The ultramarathoner's heart

The ultramarathoner's heart

Nuttall-trail 2-webThe manufacturer’s warranty on the human heart is about 100 years or 2.5 billion beats. But do ultra-long-distance runners void this warranty when they regularly run races of 50 to 100 miles?

This was the question at the top of my mind as I wrote a tall tale about Mike Nuttall, a visionary Silicon Valley product designer and an ultramarathoner with hereditary heart disease, featured in the cardiovascular health issue of Stanford Medicine. In 2010 he had a heart attack and a triple bypass operation. Then he went on to run one of the most challenging races on the planet.

Was this fearlessness or folly?

An ultramarathoner pushes a body to its outer limits. Bones and joints are pounded. Dehydration can upset the electrolyte system, the delicate balance of salts and fluids that regulates heart, nerve and muscle functions. The heart, the ultramarathoner of organs, goes into overdrive for about 24 hours. But above all, an ultramarathon tests the mind, as a runner strives to override the brain’s overwhelming signals of pain and fatigue.

In the story, there are plenty of opinions from friends and heart experts on the wisdom of Nuttall’s post-heart-attack decision. But I guess, in the end, what he did was personal and heartfelt.

Previously: Study reveals initial findings on health of most extreme runners, Euan Ashley, MD, on personalized medicine for heart disease and Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions
Photo by Bert Keely (Nuttall’s wingman)

In the News, Infectious Disease, Men's Health, Public Safety, Research, Stanford News

Exploring how gender affects the immune system

Exploring how gender affects the immune system

man_coldA piece published today on Slate examines how sex hormones, like estrogen and testosterone, may impact the strength of men and women’s immune systems. As noted in the article, recent research from Stanford immunologist Mark Davis, PhD, who directs Stanford’s Institute for Immunity, Transplantation and Infection, and his colleagues offers new insights on the issue:

… it’s been difficult to establish any direct link between levels of sex hormones circulating in the blood and the performance of men’s and women’s immune systems.

Recent research is now beginning to firmly establish that link. This month, a team of scientists at Stanford University has reported some of the best evidence yet that testosterone directly influences immune system function in men. The researchers took blood samples from male and female volunteers who were given a flu shot. Women had higher levels of immune system molecules circulating in their blood than men, and they produced more effective antibodies against the flu virus. And there were not only differences between men and women, but there were differences among men—the men with the weakest response to the flu shot had high levels of both testosterone and testosterone-induced enzymes, suggesting that high levels of testosterone can suppress immunity.

This finding that testosterone may dial down the immune system in humans is consistent with the results of studies of other animals, ranging from fish to chimps.

For more details on the study and why high testosterone may provide a less obvious evolutionary advantage, read this December Scope post from my colleague Bruce Goldman.

Previously: In men, a high testosterone count can mean a low immune responseAdults’ immune systems “remember” microscopic monsters they’ve seen beforeImmunology escapes from the mouse trap and Immunology meets infotech
Photo by Iain Farrell

Aging, Chronic Disease, Health and Fitness, Men's Health, Research, Women's Health

More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease

More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease

sitting_deskIf you have a lengthy daily commute, spend hours at a desk clacking on the computer, or sit for a prolonged period for other reasons, a pair of recent studies may have you leaping to your feet.

The first study, conducted by researchers at Cornell University, examined the effects of sitting for a long period of time each day over a 12-year period. Results showed that individuals who were inactive for more than 11 hours had a 12 percent higher mortality rate than those who sat for four hours or less. And don’t think you’re not at risk because you occasionally hit the gym. Cornell researcher Rebecca Seguin, PhD, explained in a Futurity post:

The assumption has been that if you’re fit and physically active, that will protect you, even if you spend a huge amount of time sitting each day… In fact, in doing so you are far less protected from negative health effects of being sedentary than you realize.

While this study focused on postmenopausal women, additional research from Kansas State University shows that the health risks of being sedentary affect both both genders. The study analyzed data on nearly 200,000 men and women ages 45 to 106 taken from a large Australian study of health and aging. The research showed that both exercising and reducing sitting time were key to improving health. MedicalXPress reports:

Even standing throughout the day—instead of sitting for hours at a time—can improve  and quality of life while reducing the risk for  such as , diabetes, heart disease, stroke, breast cancer and colon cancer, among others.

Sitting for prolonged periods of time—with little muscular contraction occurring—shuts off a molecule called lipoprotein lipase, or LPL, [Sara Rosenkranz, PhD,] said. Lipoprotein lipase helps to take in fat or triglycerides and use it for energy.

“We’re basically telling our bodies to shut down the processes that help to stimulate metabolism throughout the day and that is not good,”  [Rosenkranz] said. “Just by breaking up your , we can actually upregulate that process in the body.”

Previously: Exercise is valuable in preventing sedentary deathIs standing healthier than sitting?How sedentary behavior affects your health and Stanford hosts conference on the science of sedentary behavior 
Photo by Danny Choo

Evolution, Immunology, Infectious Disease, Men's Health, Research, Stanford News

In men, a high testosterone count can mean a low immune response

In men, a high testosterone count can mean a low immune response

alpha maleMen have deeper voices and tons more facial and body hair than women. They are (usually) bigger, stronger, and much more likely to risk their lives on a whim. I, for example, have been known to bite a full-sized salami in half with a single snap of my jaws when hungry, angry or threatened. Or just for the hell of it.

But when it comes to immune response, men are wimps. It’s well documented that, for reasons that aren’t clear, men are more susceptible to bacterial, viral, fungal and parasitic infection than women are and that men’s immune systems don’t respond as strongly as women’s to vaccinations against influenza, yellow fever, measles, hepatitis and many other infectious diseases.

A new study just published in the Proceedings of the National Academy of Sciences by immunologist Mark Davis, PhD, who directs Stanford’s Institute for Immunity, Transplantation and Infection, and his colleagues may explain why. The same steroid hormone that makes a man’s beard, bones and muscles grow operates – albeit it in a slightly indirect way – to shrink immune responsiveness. Yep, we’re talking about (sigh…) that much-maligned male molecule, testosterone. In a nutshell, high circulating testosterone levels boost the activity of a clutch of genes that, among other things, dial down the aggressiveness with which our immune systems fight back against invading pathogens.

Now why, we ask ourselves, would evolution be so perverse as to have designed a hormone that on the one hand enhances classic male secondary sexual characteristics such as muscle strength, beard growth (or antler size, as the case may be) and risk-taking propensity – the very hallmarks of the alpha male – but on the other hand wussifies men’s immune systems?

Here’s what I got from talking at length (and, I admit, in an uncharacteristically high-pitched voice) to Davis in preparation for the news release I wrote about the study:

The evolutionary selection pressure for male characteristics ranging from peacocks’ plumage to deer’s antlers to fighter pilots’ heroism is pretty obvious: Females, especially at mating-cycle peaks, prefer males with prodigious testosterone-driven traits. Davis speculates that high testosterone may provide another, less obvious evolutionary advantage… Men are prone to suffer wounds from their competitive encounters, not to mention from their traditional roles in hunting, defending kin and hauling things around, increasing their infection risk. While it’s good to have a decent immune response to pathogens, an overreaction to them — as occurs in highly virulent influenza strains, SARS, dengue and many other diseases — can be more damaging than the pathogen itself. Women, with their robust immune responses, are twice as susceptible as men to death from the systemic inflammatory overdrive called sepsis. So perhaps, Davis suggests, having a somewhat weakened (but not too weak) immune system can prove more lifesaving than life-threatening for a dominant male in the prime of life.

Previously: Best thing since sliced bread? A (potential) new diagnostic for celiac disease, Deja Vu: Adults’ immune systems “remember” microscopic monsters they’ve seen before, Immunology escapes from the mouse trap and Immunology meets infotech
Photo by Craig Sunter *Click-64*

Men's Health, Women's Health

Living with disorders of sex development

A touching story in Pacific Standard about people born as intersex individuals caught my attention today. Writer Alice Dreger begins by quoting a note she received from a man named Jim; he wrote to her about a community resource Dreger helped establish that he says “basically saved my life.” Jim was born with androgen insensitivity syndrome.

Dreger writes:

I offered to meet the next morning at the local tea place. And then I started wondering, as I often do with these out-of-the-blue communiqués, if this message was a fake. Was I being set up?

But the minute I saw Jim, I knew he was real. I knew he was real because he started crying, and couldn’t talk. It was a reaction I’d seen before among people with disorders of sex development (DSD) who had been too closeted to meet another person with their condition, but who could get up the gumption to ask to meet me. I served as a way out of the closet, and so I represented the first human they came upon when they opened the door. I always tried, in my reaction, to signal simply, “Yes, you are a fellow human, and I am glad you are here.” I always have trouble not crying myself.

Previously: Is the International Olympic Committee’s policy governing sex verification fair?Researchers challenge proposed testosterone testing in select female Olympic athletes and Bay Area’s first DSD parent support group meets this week 
Related: Stanford author explores struggles of intersex individuals, their families and doctors and Karkazis on intersex people
Via @edyong209

Aging, Cancer, Complementary Medicine, Men's Health

Practicing Qigong may help older prostate cancer survivors fight fatigue, pilot study finds

Practicing Qigong may help older prostate cancer survivors fight fatigue, pilot study finds

PEOPLE PRACTICING QIGONGRecovering from a severe illness can take a toll on a person. For older men who have survived prostate cancer and undergone androgen deprivation therapy, lingering effects may include fatigue and associated quality-0f-life issues. A small pilot study in older prostate cancer survivors has found that practicing Qigong – a gentle body-mind practice that incorporates fluid movement, deep breathing and meditation – may be a helpful non-drug tool for relieving this fatigue.

Scientists at the University of New Mexico Cancer Center and the University of North Carolina at Chapel Hill conducted the 12-week randomized controlled trial in 40 men with an average age of 72. All of the participants reported high levels of fatigue at the beginning of the study. One-half of the men engaged in Qigong classes, while the other half participated in a stretching class.

As outlined in the study (subscription required), published in the Journal of Cancer Survivorship, the researchers “found that the Qigong intervention was associated with significantly larger improvements in fatigue and distress than the stretching group.” The findings, they noted, “are consistent with other Qigong [randomized controlled trials] for cancer survivors and depressed, chronically ill older adults.”

Co-lead author Rebecca Campo, PhD, said in a release, “Qigong may be an effective nonpharmacological intervention for the management of senior prostate cancer survivors’ fatigue and distress.” She added that larger trials and ones that include racially and ethnically diverse participants are needed to confirm the results of the initial trial.

Previously: NIH hosts Twitter chat on using mind and body practices for managing holiday stress and anxietyStudy shows practicing tai chi may increase brain volume in healthy older adults and Study examines the benefits of Tai Chi for the elderly
Photo by ASSOCIATED PRESS

Ask Stanford Med, Fertility, Men's Health, Pregnancy, Stanford News, Women's Health

Ask Stanford Med: Expert in reproductive medicine responds to questions on infertility

Ask Stanford Med: Expert in reproductive medicine responds to questions on infertility

couple sitting2Infertility is a reality faced by 10 to 15 percent of U.S. couples. For some, the topic is emotionally charged. And while many may have questions related to reproductive endocrinology, research and treatment options may not be favorite table topics for a night out with friends. So for this edition of Ask Stanford Med, we’ve asked Valerie Baker, MD, the division chief of reproductive endocrinology and infertility and director of Stanford’s Program for Primary Ovarian Insufficiency, to respond to such questions about infertility. Her answers appear below.

@giasison asks: Can you name the 3 top causes of #infertility in your current practice?

Age-related decline in fertility (particularly decline in egg quantity and egg quality with age), sperm problems, and lack of ovulation.

Charmaine asks: Is it true that infertility could be a side effect of vaccination? Why?

No, vaccinations do not cause infertility.

Michelle asks: How have treatments for infertility evolved over the last 10 years? And what might treatments look like 10 years from now?

The biggest advance since the mid-90s has been our ability to help couples with extremely poor sperm quality to conceive. I hope that 10 years from now we will have treatments that help couples where a woman is suffering from premature loss of her egg supply to conceive with her own eggs. Right now, the main choice for women with extremely low egg supply and low egg quality is oocyte donation, where the egg comes from a donor.

Shabba92 asks: What are the most common treatments in your clinic? What percentage of patients wind up undergoing IVF?

The most common treatments are intrauterine insemination (IUI) and in vitro fertilization (IVF). We also do ovulation induction for women who are not ovulating on their own and surgery if needed to correct certain problems. Many couples are able to conceive with simpler treatments and do not need IVF. Fewer than half need IVF.

Continue Reading »

Men's Health, Public Health, Research, Rural Health, Stanford News

A guide to coping with a common male birth defect

A guide to coping with a common male birth defect

One of the most common birth defects in boys occurs when the urethral tube fails to completely close, leaving the urethral opening somewhere along the underside of the penis, rather than the tip. Approximately one in 200 males is born with the condition, but the cause is usually unknown. It’s been suggested that exposure to pesticides might be the culprit in some cases, but no definitive studies have been done.

A paper from Stanford researchers, which came out today in the journal Pediatrics, presents results of analyses they conducted of several hundred pesticides commonly used in commercial applications. They found weak links with 15 of the chemicals, but emphasize that further studies need to be done before anyone can say there’s a link between any of the chemicals and the condition, called hypospadias. You can read more of the details in our press release.

Causation aside, parents of a baby boy born with the condition have to make decisions about how to treat the condition.

“Any birth defect is concerning to parents, and a defect in the genital structure often causes special concern,” William Kennedy, MD, associate professor of urology at Stanford and associate chief of pediatric urology at Lucile Packard Children’s Hospital, told me.

Kennedy has been counseling parents and performing corrective surgeries for years and has seen the difficulty parents often have in dealing with the condition.

“Parents are often reluctant to talk to anyone — even medical professionals — about the baby’s condition,” Kennedy added. “Fortunately, most corrective surgeries have positive outcomes.”

Kennedy says a lot of parents first turn to the Internet for information and, as we all know, sometimes what we find there can be misleading. That prompted Kennedy and Suzan Carmichael, PhD, associate professor of pediatrics and lead author of the Pediatrics study, to join with Matt Dorow, who has a son born with the condition, to write a book on
the subject for parents.

“Hypospadias – A Guide to Treatment,” is a slender volume of just over 100 pages, containing information and guidance on every aspect of hypospadias. The recently published book presents information in a clear, organized fashion and includes short pieces written by a man born with the condition and Dorow. If you have a boy born with hypospadias, or know someone who does, it could be immensely helpful.

Health and Fitness, In the News, Men's Health, Mental Health

Story highlights need to change the way we view and diagnose eating disorders in men

Story highlights need to change the way we view and diagnose eating disorders in men

Previously on Scope, we’ve discussed how eating disorders, such as anorexia and binge eating, are increasingly being recognized in men. But why? As a story in today’s San Francisco Chronicle explains, this increase is probably due to a combination of factors.

The story tells how two men grapple with anorexia and highlights two Stanford researchers who study eating disorders in men and women. Though their collective experiences, we learn how the notion that eating disorders are a “female problem” could predispose family members, medical professionals, and even people with eating disorders to overlook the disease in men. From the piece:

“Even males with eating disorders think of anorexia as a female problem in which the main goal is to be thinner,” said Alison Darcy, a psychiatry research associate at Stanford who has been among those leading a charge to gain greater recognition for male disorders.

Darcy recently led a study of adolescent boys with eating disorders at Stanford’s Eating Disorder Program. As the article explains, Darcy found that many young boys with eating disorders want a lean and muscular physique, rather than just weight loss.

One important aspect of Darcy’s study is simply that it focuses on eating disorders in young boys. Research on eating disorders tends to be “gender-biased, with many studies still focusing exclusively on women and girls,” according to the piece.

“If we continue to act as though eating disorders do not occur in men, we are missing a vast population of need,” Athena Robinson, PhD, a Stanford psychologist, commented.

Previously: KQED health program examines causes and effects of disordered eatingWhat a teenager wishes her parents knew about eating disorders and Stanford’s eating disorder program owes its success to holistic treatment

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