Alzheimer’s Research Takes a New Turn

Study suggests that gummed-up synapses — not plaque — may be at the root of aging brain diseases

A protein that accumulates in healthy aging brains could prove to be the culprit behind the natural forgetfulness that comes with growing old as well as advanced neurodegenerative diseases such as Alzheimer’s, according to a new study.
The protein, known as C1q, accumulates on the brain’s synapses as people age, potentially gumming up the works, said Dr. Ben Barres, professor and chair of neurobiology at the Stanford University School of Medicine and senior author of the study, published Aug. 14 in the Journal of Neuroscience.
A post-mortem review of mouse and human brains found that the amount of C1q in the brain increases as much as 300-fold with aging.
By comparing brain tissue from mice of varying ages as well as postmortem samples from a 2-month-old infant and an older person, the researchers found that the growing C1q deposits weren’t randomly distributed along nerve cells.
Instead, they heavily concentrate at synapses (the junctions between nerve cells), where they could hamper the conduction of electrical and chemical signals in the brain.
“Synapses are not being lost,” Barres said. “However, we see the synapses aren’t working so good with all that C1q stuck to them. It’s detrimental.”
But C1q is known to play an important part in the developing brain during childhood, and Barres suspects that this function could lead the protein to attack the synapses if triggered. Such an attack could be the cause of Alzheimer’s disease and other neurodegenerative disorders.
This hypothesis runs counter to prevailing theories about Alzheimer’s, which have focused on the accumulation of amyloid plaques in the brain as a cause of the disease.
In a normal developing brain, synapses are both created and destroyed — a process Barres likens to “pruning” the brain by preserving necessary synapses and eliminating the excess.
“What wasn’t clear is what the molecular basis of the synapse pruning was,” Barres said. “It involves a normal immune protein that people didn’t even realize was in the brain — C1q.”
C1q is capable of clinging to the surface of foreign bodies such as bacteria or to bits of dead or dying human cells. This initiates a molecular chain reaction known as the complement cascade. One by one, the system’s other proteins glom on, coating the offending cell or piece of debris. This in turn draws the attention of omnivorous immune cells that gobble up the target.
Barres now hypothesizes that diseases such as Alzheimer’s might develop if the C1q that has accumulated on the synapses triggers an immune system attack against them.
“The first regions of the brain to show a dramatic increase in C1q are places like the hippocampus and substantia nigra, the precise brain regions most vulnerable to neurodegenerative diseases like Alzheimer’s and Parkinson’s disease, respectively,” Barres said. Another region affected early on, the piriform cortex, is associated with the sense of smell, whose loss often heralds the onset of neurodegenerative disease.
“Our findings may well explain the long-mysterious vulnerability specifically of the aging brain to neurodegenerative disease,” he said. “Kids don’t get Alzheimer’s or Parkinson’s,” Barres pointed out.
“Profound activation of the complement cascade, associated with massive synapse loss, is the cardinal feature of Alzheimer’s disease and many other neurodegenerative disorders. People have thought this was because synapse loss triggers inflammation. But our findings here suggest that activation of the complement cascade is driving synapse loss, not the other way around,” Barres explained.
Heather Snyder, director of medical and scientific operations for the Alzheimer’s Association, said the new study “adds to the body of information that looks at how the immune system might work in Alzheimer’s disease.” She added that there are many hypotheses that need to be explored about what may be happening in Alzheimer’s.
Noting that much of the research in the current study involved mice, Snyder said future studies need to focus on how C1q affects human brains.
“This is really opening the door that this should be explored further,” she said. “It needs to be replicated in the laboratory and also correlated to what it may mean in human beings.”
More than 5 million Americans have Alzheimer’s disease, and that number is expected to rise significantly as the baby boom generation ages.
SOURCES: Ben Barres, M.D., Ph.D., professor and chair, neurobiology, Stanford University School of Medicine, Stanford, Calif.; Heather Snyder, director, medical and scientific operations, Alzheimer’s Association; Aug. 14, 2013, Journal of Neuroscience

Breastfeeding could be good not only for the baby but also for the mother

Could breastfeeding be as good for a Mom’s health as it is for her babies? A new study in the Journal of Clinical Nursing looks at the relationship between breast cancer and certain features of pregnancy and breastfeeding.
The researchers collected data from the medical records of more than 500 women who were diagnosed with breast cancer from 2004 to 2009. The women were 19 to 91 years of age. The team looked at age of diagnosis, how long the women breastfed, family history of cancer, obesity, alcohol consumption and smoking habits.
The results: women who breastfed were diagnosed with breast cancer at a later age, regardless of family history.
Nonsmokers who breastfed for more than six months were diagnosed much later in life – an average 10 years later than nonsmokers who breastfed for a shorter period.
Smokers, on the other hand, were diagnosed with breast cancer at a younger age and saw no significant benefit from longer breastfeeding.
The researchers say their findings show that longer breastfeeding is not only beneficial for children, but may protect mothers against the serious disease like breast cancer.

Ruling Out Unneeded Ankle X-Rays for Kids

Applying simple rule for low-risk injuries helped ER docs cut use by 22 percent

By using a simple rule to assess children’s ankle injuries, doctors could reduce the use of X-rays by 22 percent — and so spare kids unneeded radiation exposure, according to a new study.
The research appears in the current issue of the CMAJ (Canadian Medical Association Journal). While X-rays are used to diagnose 85 percent to 95 percent of ankle injuries in children, only 12 percent of X-rays show fractures, according to a journal news release.
“Radiography is unnecessary for most children’s ankle injuries, and these high rates of radiography needlessly expose children to radiation and are a questionable use of resources,” wrote Dr. Kathy Boutis, a pediatric emergency department physician at the Hospital for Sick Children and the University of Toronto, and colleagues.
The investigators applied the “low risk ankle rule” in more than 2,100 children, aged 3 to 16, who arrived at six Canadian emergency departments with non-penetrating ankle injuries.
The rule states that if an examination of a child’s injured ankle suggests that there is a low risk of fracture, an X-ray may not be necessary. If doctors miss a certain category of fractures, evidence shows that they are stable, pose a low risk for any future problems, and can be treated like an ankle sprain.
The 22 percent reduction in the use of X-rays when using the rule was consistent in the different emergency departments.
“The ankle rule has potential broad applicability to emergency departments throughout most of the developed world, and widespread implementation of this rule could safely lead to reduction of unnecessary radiography in this radiosensitive population and a more efficient use of health care resources,” the researchers concluded.
SOURCE: CMAJ (Canadian Medical Association Journal), news release, Aug. 12, 2013

Pregnant and Obese: Early Deaths Noted Among Offspring

Study findings suggest need for weight control before conception

Here’s another reason for young women to get their bad eating habits under control: Kids born to obese mothers are likely to die earlier than those born to normal-weight mothers, a new Scottish study suggests.
In the United States and Europe, about two-thirds of women of reproductive age are overweight and more than one-third are obese, according to the study. Previous research has suggested that obesity during pregnancy may boost the risk of high blood pressure and high blood sugar, which are linked to cardiovascular disease, in their offspring. The findings of the new study are even more ominous.
“We need to think about targeting children of obese mothers for lifestyle interventions to maintain a healthy weight,” said study author Rebecca Reynolds, a professor of metabolic medicine at the University of Edinburgh.
But the findings aren’t conclusive, and it could be that the mothers’ weight has nothing to do with the life spans of their children. It’s possible, for example, that families with poor diets produce heavier moms and sicker kids.
Also, even if the link is confirmed, it’s not clear if these offspring can alter their extra risk of dying earlier, the researchers added.
Earlier this year, a committee of the American College of Obstetricians and Gynecologists said all overweight or obese women should be offered nutrition counseling and be encouraged to follow an exercise program.
But the results of the new study suggest that weight-loss interventions should begin before pregnancy, according to Pam Factor-Litvak, author of an accompanying journal editorial.
For the study, published online Aug. 13 in the journal BMJ, the researchers tracked almost 38,000 people born in Scotland from 1950 onward who were aged 34 to 61 in 2011. They looked for data on the mothers body-mass index (BMI) — a measurement of body fat based on height and weight — and any deaths or heart disease among their children through that year.
Overall, more than 6,500 deaths from any cause were reported, and the leading causes of death were cardiovascular disease and cancer.
Those whose mothers were obese at birth — meaning they had a BMI of 30 or higher — were 35 percent more likely to have died by 2011 than those whose mothers were a normal weight.
These young and middle-aged adults were also about 29 percent more likely to have been admitted to a hospital because of a heart problem; overall, 8 percent were admitted for that reason.
The researchers came up with these numbers after adjusting their statistics to account for factors such as income level, gender, or maternal age at birth.
Children of mothers who were overweight — a BMI of 25 to 29 — were 11 percent more likely to die than those of mothers of normal weight.
The mechanisms behind this association aren’t clear, and the researchers were lacking one crucial piece of information: whether the kids of obese pregnant moms became obese themselves. However, Reynolds said it’s possible that genes play a role. Or, it’s possible that the families of obese pregnant moms had poor eating habits that affected their children’s health later on.
Shinga Feresu, an associate professor at Indiana University School of Public Health, said it’s also possible that health conditions such as diabetes, kidney disease and high blood pressure could have thrown off the results. Overweight and obese children and teens are more likely to develop type 2 diabetes, putting them at a higher risk of early heart disease, Feresu said.
Nonetheless, it’s clear that “women who are obese need to reduce their weight to a healthy level before they become pregnant,” Feresu said. “They will have a much healthier baby, with reduced risk of long-term disease and premature death.”
Previous research has highlighted other obesity-related pregnancy problems. A study published in June in the Journal of the American Medical Association found that overweight or obese women who are pregnant are more likely to give birth prematurely, and the risk of preterm delivery increases with their amount of excess weight.
SOURCES: Rebecca Reynolds, Ph.D., professor, metabolic medicine, University of Edinburgh, Scotland; Shinga Feresu, Ph.D., MPH, associate professor, epidemiology, biostatistics and medicine, Indiana University School of Public Health, Bloomington, Ind.; Aug. 13, 2013, BMJ, online

Many Risk Factors for Early Dementia Can Show Up in Teens

Alcohol abuse topped the list in large study of Swedish men

Swedish researchers have identified nine risk factors — many occurring during a person’s teens — that are tied to early onset dementia.
The good news is that several of these symptoms and behaviors can be prevented or treated, experts noted.
Early onset (or young-onset) dementia occurs before the age of 65. Alcohol abuse was the most important risk factor found in the study, said lead researcher Peter Nordstrom. “In contrast, the influence of hereditary factors, that is dementia in the parents, was very small.”
For the study, published online Aug. 12 in the journal JAMA Internal Medicine, Nordstrom’s group collected data on men drafted into the Swedish military from mid-1969 through 1979. They were about 18 years old when they were drafted.
During the follow-up period of roughly 37 years, 487 men developed young-onset dementia at an average age of 54, the researchers found.
The risk factors identified “were multiplicative, most were potentially modifiable and could be traced to adolescence, suggesting excellent opportunities for early prevention,” said Nordstrom, from the department of community medicine and rehabilitation at Umea University
Alcohol intoxication, stroke, use of antipsychotic drugs, depression, drug abuse, a father with dementia, poor mental function as a teen, being short and having high blood pressure were the risk factors they found.
Taken together, these accounted for 68 percent of the cases of young-onset dementia, the researchers said. Men with at least two risk factors and in the lowest third of overall mental ability had a 20-fold increased risk.
“Young-onset dementia, before age 65, is a devastating condition for patients and their families,” said Dr. Deborah Levine, an assistant professor of medicine at the University of Michigan and author of an accompanying journal editorial.
One priority for young-onset dementia is research that identifies ways to prevent it, she said. Another is to improve care and access to long-term services for adults who are diagnosed with dementia before 65.
“This is urgent because adults with young-onset dementia and their families really need our help,” she said. “More Americans may develop young-onset dementia because of increases in traumatic brain injury among young veterans and stroke among young African-Americans and middle-aged adults.”
Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health in New York City, said the new study is “extraordinary and deserves attention by others studying adolescent populations to see whether this Swedish experience can be confirmed elsewhere and independently.
“I always prefer to see replication of data — especially ‘game-changing’ data like these — before I sound any alarm, but given the treatability of these risks, I would say that these observations should prompt aggressive attention by physicians with access to adolescents,” Gandy said.
Dementia affects an estimated 35 million people worldwide and is expected to rise sharply by 2050, according to study background information.
SOURCES: Peter Nordstrom, Ph.D., department of community medicine and rehabilitation, Umea University, Sweden; Deborah Levine, M.D., M.P.H., assistant professor, medicine, University of Michigan, Ann Arbor; Sam Gandy, M.D., Ph.D., director, Mount Sinai Center for Cognitive Health, New York City; Aug. 12, 2013, JAMA Internal Medicine, online

Eye Photography May Reveal Stroke Risk, Study Finds

Your eyes may provide a window into your risk for a stroke, a new study suggests.
By photographing the retina, researchers say they can predict the potential for stroke in people with high blood pressure.
“High blood pressure is one of the most important factors involved in the development of stroke,” said lead researcher Dr. Mohammad Kamran Ikram, an assistant professor at the Singapore Eye Research Institute of the National University of Singapore. But determining which hypertensive patients face the highest risk of stroke isn’t possible.
Now, a simple eye examination may provide that information, Ikram said. He said, however, that other studies are needed to confirm the findings, which were published Aug. 12 in the journalĀ Hypertension.
High blood pressure can damage blood vessels in the retina. When that happens, the condition is known as hypertensive retinopathy. Retinal imaging is a non-invasive way to view blood vessel damage and possibly assess risk for stroke, a leading killer of Americans.
Stroke occurs when blood flow to the brain stops, either because of a clot or a hemorrhage.
One expert, Dr. Ralph Sacco, chairman of neurology at the University of Miami Miller School of Medicine, welcomed the study results. He said the findings add to previous research on the value of retinopathy as an indicator of small vessel disease and increased risk of stroke.
“More aggressive management of blood pressure may be needed in patients with signs of retinopathy in order to reduce stroke risk,” Sacco said.
“We often do not pay enough attention to even mild to moderate findings on a retina exam and should include this assessment in our global evaluation of vascular and stroke risk,” he added.
For the study, Ikram’s team followed nearly 3,000 people with high blood pressure for an average of 13 years. At the start of the study, each participant had photos taken of their retinas — the light-sensitive layer of cells at the back of the eye.
The researchers rated each patient’s hypertensive retinopathy as none, mild or moderate/severe based on the damage evident in the photographs.
During the follow-up period, 165 participants suffered a stroke. The researchers found those with mild hypertensive retinopathy had a 35 percent higher risk for stroke, while those with moderate or severe retinopathy had a 137 percent increased risk.
Retinal damage also predicted increased risk for stroke in patients taking medication to keep their blood pressure under control, the researchers found. In this group, mild hypertensive retinopathy corresponded with a 96 percent increased risk for stroke and for those with moderate to severe hypertensive retinopathy, a 198 percent increased risk.
The risk for stroke remained even after taking into account factors such as age, sex, race, cholesterol levels, smoking, blood pressure readings and body-mass index (a measurement of body fat based on height and weight), the researchers said.
Although the researchers found an apparent link between retinal damage and increased stroke risk, the study did not prove a definitive cause-and-effect relationship.
Although these results are preliminary and need to be replicated, they suggest that retinal imaging could be a good addition to a stroke-risk evaluation, said Dr. Floyd Warren, chief of neuro-ophthalmology at Lenox Hill Hospital in New York City.
“There may be a need for more aggressive blood pressure management,” he said.
SOURCES: Mohammad Kamran Ikram, M.D., Ph.D., assistant professor, Singapore Eye Research Institute, National University of Singapore; Floyd Warren, M.D., chief, neuro-ophthalmology, Lenox Hill Hospital, New York City; Ralph Sacco, M.D., chairman, neurology, University of Miami Miller School of Medicine.

Earlier Acne Outbreaks May Be Caused by Earlier Puberty: Experts

New guidelines released to help doctors treat younger patients age-appropriately

Though acne has long been viewed as a teen phenomenon, dermatologists have been tending to an ever-younger patient pool, a new preadolescent reality that many experts link to a trend toward an earlier onset of puberty.
Now, a team of physicians has put together a new list of treatment recommendations that they hope will lead to a better age-appropriate standard of care for children as young as 7.
The guidelines address issues such as when over-the-counter creams should be used versus prescription medicines (including antibiotics, retinoids and, for girls in some cases, hormone therapy). They also discuss how to help young patients stick with their treatments and deal with the emotional effects of acne.
“As the initial start of puberty is occurring earlier than in the past, we needed to define the age ranges and concerns regarding the different groups that make up pediatric acne,” said guideline co-author Dr. Andrea Zaenglein, a pediatric dermatologist and professor of dermatology and pediatrics at Penn State/Hershey Medical Center.
She said the goal is “to provide pediatricians and anyone who cares for children with acne with specific guidelines for the care of their patients.”
Zaenglein and her colleagues presented their recommendations, which have been endorsed by the American Academy of Pediatrics and published in Pediatrics, at the recent American Academy of Dermatology annual meeting in New York City.
The team defines preadolescent acne as cases occurring among children aged 7 to 12.
The guideline authors pointed out that preadolescent acne is not usually a cause for undue alarm, typically involving the onset of whiteheads and blackheads in the forehead, nose and chin region. More serious inflammatory lesions are not commonly seen among these younger patients, and scarring — though a concern — is rare.
The new recommendations advise doctors to first treat cases of preadolescent mild acne with over-the-counter benzoyl peroxide. Only when such products fail to do the trick — or when children are afflicted with larger-than-usual acne zones — are age-appropriate oral antibiotics or retinoids to be added to the treatment.
Children should also be instructed to adopt good cleansing protocols, such as washing acne-prone areas twice daily with a nonabrasive pH-balanced cleanser.
Consistent monitoring alongside treatment is also suggested even once acne is brought under control, as the onset of preadolescent acne can be an early sign of more serious acne problems as a child ages into a teen and young adult.
While acknowledging the need to identify the problem and seek appropriate treatment, Zaenglein stressed that “it is important that parents do not panic” because preadolescent acne is readily controllable.
“Acne is very unlikely to be a sign of a hormonal abnormality in that age range,” she said, “although your doctor should confirm with a thorough history and physical exam.”
But what explains the preadolescent acne phenomenon in the first place?
The jury is still out, said Dr. Lawrence Eichenfield, chief of pediatric and adolescent dermatology at the University of California, San Diego (UCSD), and himself a member of the guideline team.
“There are many ideas as to why this is happening,” he said. “It is true that while back in the 1990s it was not that uncommon to see the onset of puberty among 8- or 9-year-olds, there is good data that children are, in fact, going into puberty now about one year earlier than was the case 20 years ago,” Eichenfield explained.
“So it could be about hormones, about nutrition, about the obesity epidemic,” he suggested. “But I would call these ideas, not even theories. We really just don’t know what the reason is. But what we do know is that it’s not happening just in the U.S. This is a worldwide phenomenon,” he added.
“Which is why I’m very pleased that now, for the first time, we have evidence-based guidelines for the treatment of pediatric care,” Eichenfield said. “And that means that parents should feel comfortable that their pediatricians and dermatologists will now have consistent and reliable ways to treat children, and minimize the negative physical and psychological impact that acne can come to have over a patient’s lifetime.”
For her part, Dr. Sheila Friedlander, a pediatric dermatologist and clinical professor of pediatrics and medicine at UCSD, expressed hope that the new recommendations will help caregivers guide parents away from the “perfect storm of anxiety” that can arise when confronted with preadolescent acne.
“As long as no other signs of a problem exist, such as significant armpit/groin hair or breast development, we consider this ‘early acne’ a normal event,” she said.
“Therefore, health care givers must be prepared to provide parents with an appropriate approach to acne,” Friedlander added, agreeing that most cases are eminently treatable when handled properly.
SOURCES: Andrea Zaenglein, M.D., FAAD, pediatric dermatologist, and professor, dermatology and pediatrics, Penn State/Hershey Medical Center; Sheila Friedlander, M.D., pediatric dermatologist, and clinical professor, pediatrics and medicine, department of medicine, University of California, San Diego; Lawrence Eichenfield, M.D., chief, pediatric and adolescent dermatology, University of California, San Diego; July 31-Aug. 4, 2013, American Academy of Dermatology annual meeting, New York City; May 2013 Pediatrics