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Thursday, November 19, 2015
BY REBECCA HISCOTT
In 1983, the life expectancy for a person with Down syndrome—a genetic disorder that causes low muscle tone, small stature, and an upward slant to the eyes, as well as developmental or cognitive delays—was age 25. Today, thanks to advances in medical technology, people with Down syndrome are living longer, with 80 percent living to age 60. But this as people with Down syndrome live longer, so too do they face an increased risk for Alzheimer's.
New Research Projects
The National Institutes of Health (NIH) announced Wednesday that it’s supporting two large-scale research projects to study the progression of Alzheimer’s disease in people with Down syndrome and identify biological markers (or biomarkers) in the blood and cerebrospinal fluid that may signal the risk, onset, and progression of Alzheimer’s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Aging at the NIH will provide an estimated $37 million over five years to support the projects.
People with Down syndrome are born with an extra copy of chromosome 21, which contains the amyloid precursor protein (APP) gene, according to the NIH. This gene is linked to the production of beta-amyloid protein; when too much of this protein accumulates in the brain, it can form the sticky plaques that accumulate in nerve cells in Alzheimer’s disease. Having three copies of the APP gene is a known risk factor for developing early-onset Alzheimer’s.
By age 40, most people with Down syndrome have these plaques in their brains, the NIH says, along with twisted tangles of tau protein, another hallmark of Alzheimer’s disease. Not all of those with plaques and tangles in the brain will go on to develop Alzheimer’s, but the NIH estimates that at least half of people with Down syndrome will develop dementia due to Alzheimer’s disease as they age into their 70s. Many begin to show symptoms in their 50s and 60s. Given the presence of amyloid and tau in autopsied brain tissue, scientists want to find out why some, but not all, people with Down syndrome develop Alzheimer's.
The Hunt for Biomarkers
The new studies, which will involve researchers from all over the country, will use positron emission tomography (PET) and magnetic resonance imaging (MRI) scans to track levels of the amyloid and tau proteins in the blood and cerebrospinal fluid of participants and measure brain volume and function. The researchers will also administer blood tests to look for genetic factors involved in Alzheimer’s risk and identify blood-based markers of the disease, as well as a battery of cognitive and memory tests to measure changes in behavior and cognitive function.
“These are the first large-scale efforts to identify the progression of clinical, cognitive, imaging, genetic, and biochemical biomarkers of Alzheimer’s disease in Down syndrome,” Laurie Ryan, PhD, chief of the Dementias of Aging Branch in the NIA’s Division of Neuroscience, told Neurology Now in an email.
The hope is that researchers will one day be able to use these biomarkers to evaluate the effectiveness of new treatments, she said.
For more information about Down syndrome and Alzheimer’s disease, visit the NIH’s resource page. To learn more about Down syndrome, go to the National Down Syndrome Society website. For articles about Alzheimer’s disease and dementia, browse our archives here.
Image by Vanellus Foto (Own work) [GFDL or CC BY-SA 3.0], via Wikimedia Commons.
Monday, November 02, 2015
BY RAGHAV GOVINDARAJAN, MD
Lisa was a vivacious 40-year-old when she was diagnosed with amyotrophic lateral sclerosis (ALS). Over the next two years, she went from managing a cosmetics store to being completely wheelchair-bound. During every visit, her husband asked me if there was a cure, and every time my answer was the same: “No.”
Despite many advances in medicine, treatment for ALS remains elusive—and several factors complicate the search for a cure. I’ll try to provide clarity on some of those factors.
ALS is rarely inherited. Only 5 to 10 percent of cases are passed down from families. The other 90 to 95 percent are sporadic, meaning people get the disease randomly. Some genes have been found that are linked to the disease, including the SOD1 and C9ORF72 genes. Researchers have learned that different genes cause different manifestations of the disease, which may require different treatments. This adds a whole new layer of complexity to finding a cure.
Unreliable Lab Rats
Before drugs are tested in humans, they are often tested in rats or mice in the hopes that the results will translate to humans. Typically, researchers first inject mice with disease-causing genes. Then, they inject various drug molecules to see if those molecules stop the disease or slow its progression. Unfortunately, many drugs that have worked in mice fail to produce the same results in human trials.
The gold standard for human trials is the double-blind study, which is designed so that neither the patient nor the doctor knows who is taking the drug and who is getting the placebo. This ensures that conclusions drawn from the study are valid and free from bias. Many trials using lab animals are done without adequate blinding, potentially exaggerating the results. In some cases, when adequate blinding was applied to animal studies, the results weren’t as dramatic as initially claimed, or the drug molecules actually worsened the disease.
Biomarkers are signals in the blood or body that indicate disease activity. So, for instance, high cholesterol is considered a biomarker for stroke or heart disease. In ALS, doctors look for biomarkers using the ALS Functional Rating Scale, which measures changes in physical functioning due to the disease. They also measure muscle strength and breathing capacity using various devices. These biomarkers aren’t sensitive enough to measure disease activity during a clinical trial, however. By the time researchers see changes in these measurements, the disease may be too advanced; if the drug hasn’t worked, much time and effort will have been wasted. So far, no clinical trial for ALS has been able to determine whether the drug reached its intended target (whether the target is a cell, a protein, or a specific gene), if the drug levels in the blood were adequate, or if the drug did what it was supposed to do.
Poor Trial Design
In the race to find a cure, many doctors and researchers have tested various types of drugs on ALS patients. Many of these trials are small and poorly designed, and only add muddled data. Equally concerning are disreputable quacks offering snake oil in the form of unproven stem cell therapy, fleecing patients of their life savings.
Another challenge is delayed diagnosis. Patients often see several doctors before getting an official diagnosis, in part because there is no simple diagnostic test for ALS. By the time patients enter a clinical trial, their disease may be too advanced for the drug to work.
As scientists continue to look for a cure for ALS, I encourage people like Lisa to seek multidisciplinary care from a team of compassionate physicians who can improve their quality of life. And despite some of the challenges in ALS clinical trials, I still urge people with ALS to consider enrolling to get the best possible care and to propel research forward.
Check back soon for an article where I’ll share the top advances in ALS research, which might one day lead to a cure for this devastating disease.
Ask Dr. G: If you have a question for Dr. Govindarajan, a neurologist at the University of Missouri in Columbia, MO, please click here.
Wednesday, October 21, 2015
BY REBECCA HISCOTT
People with multiple sclerosis (MS) who soaked up sun in their teenage years and stayed trim in their 20s developed the disease later than people who were overweight in their 20s or spent less time outdoors in their teens, researchers reported in a new study in Neurology.
The study adds to past research showing that exposure to sunshine and high levels of vitamin D (which people get mainly from the sun) can affect MS symptoms and onset, they said.
Researchers in Denmark evaluated 1,161 Danish people with MS between 2009 and 2012. The participants, who were all enrolled in a national registry for MS, completed questionnaires asking about a number of factors early in life, including how much time they spent in the sun during their teenage years and how much they weighed at age 20. (The researchers excluded study participants who had been diagnosed with MS before age 20.)
More Sun, Less Weight Linked to MS Delay
People who said they spent time in the sun every day as teenagers developed MS an average of 1.9 years later (around age 32.9) than those who had spent less time in the sun, who were diagnosed around age 31.
The researchers also found that people who were overweight at age 20 (defined as a body mass index [BMI] over 25) developed the disease 1.6 years earlier than those who were of a normal weight (a BMI of 18.5 to 24.9) and 3.1 years earlier than those who were underweight (a BMI of less than 18.5).
Vitamin D and MS
Sunlight is one of the main sources of vitamin D, and higher levels of vitamin D have been shown to protect against MS symptoms and even lower the risk of developing the condition, the researchers noted. But it’s also possible that sunshine delays MS independently of its effect on vitamin D, they said.
“The factors that lead to developing MS are complex and we are still working to understand them all. This study suggests that sun exposure during the teenage years may even affect the age of onset of the disease, but it’s possible that other outdoor factors play a role, and these still have to be identified,” said study author Julie Hejgaard Laursen, MD, PhD, a researcher at Copenhagen University Hospital, in a news release.
The relationship between weight and MS also might be explained by a vitamin D deficiency, Dr. Laursen added. People who are obese tend to have lower levels of vitamin D, the researchers noted in their study. “But there’s not enough direct evidence to establish this yet,” Dr. Laursen said.
The study only included Danish participants, so results may not translate to people living in other parts of the world or of other ethnicities, the researchers warned.
Recall bias could be another problem. Study participants were asked to report on early-life factors many years and even decades later, and it’s possible that they misremembered certain facts, the researchers cautioned. These are all factors that need to be tackled in future research.
To learn more about MS, read The Basics. For more articles about MS, browse our archives.
Image via John Morgan on Flickr.
Tuesday, October 20, 2015
A phase 2 clinical trial is currently recruiting participants to test a new drug that may protect neurons against Alzheimer’s disease.
BY GINA SHAW
Many drugs used to treat Alzheimer’s disease target beta-amyloid, the toxic protein fragment that forms plaques between the brain’s delicate, vital neurons—the cells that process and transmit information. As more of these plaques accumulate, once-healthy neurons begin to deteriorate, lose their ability to function and communicate, and ultimately die.
A new phase 2 clinical trial called the NOBLE study is testing T-817MA, a compound that appears, in animal studies, to shield neurons from amyloid toxicity, says Laurie Ryan, PhD, chief of the Dementias of Aging branch in the division of neuroscience at the National Institute on Aging (NIA). (The NIA supports the Alzheimer’s Disease Cooperative Study, or ADCS, the consortium running the trial, but is not funding it directly; all financial support comes from the drug’s manufacturer, Toyama Chemical Co.)
New Drug with Novel Properties
In addition to its neuroprotective effect, T-817MA seems to be neurotrophic as well, which means “it makes new connections between cells,” says Robert Stern, PhD, director of the Clinical Core at Boston University’s Alzheimer’s Disease Center and an investigator for the NOBLE study. That neuroprotective and neurotrophic combination is rare, Dr. Stern says.
It's also promising that T-817MA is an entirely new drug, Dr. Ryan says. “Repurposing existing drugs or compounds that have been tested in other diseases happens often, and it's great. But this is a novel compound that was found to have these properties.”
Another important factor is that the trial focuses on the mild to moderate stages of the disease, says James Hendrix, PhD, director of Global Science Initiatives for the Alzheimer’s Association. “Prevention trials and studies targeting early-stage disease are exciting, but they won't help people whose disease has already progressed.”
How to Volunteer
To participate in the study, you must:
· Be aged 55 to 85 years old and have a diagnosis of mild to moderate Alzheimer’s disease;
· Live in the community (either at home or in an independent living facility, but not in a nursing home);
· Be stable on either on Aricept (donepezil) or the Exelon Patch (rivastigimine);
· Have a study partner (such as a spouse, adult child, or other companion or caregiver) who has at least 10 hours of contact with the participant weekly, and who can attend study visits;
· Weigh no more than 220 pounds;
· Commit to approximately 12 to 14 office visits that may last a couple of hours or most of the day;
· Take medication daily and consistently, and save the packaging to bring back for the next visit in order to keep track of the medication;
· Agree to regular imaging scans; people who cannot undergo an MRI because they have metal in their body, such as a pacemaker or a surgical implant, would have CT scans instead.
To find a NOBLE study location near you, go to noblestudy.org.
Friday, October 16, 2015
BY REBECCA HISCOTT
Waitresses and nurses aids, take note: Your stressful job may be increasing your risk for stroke, according to a new study in Neurology. The risk appears to be highest for ischemic stroke, which occurs as a result of a blood clot blocking the flow of oxygen to the brain, and pertains mostly to women, according to the researchers.
Analyzing Job Types
Chinese researchers analyzed every published high-quality research study on job strain and stroke risk. They identified six that involved a total of 138,782 participants who ranged in age from 18 to 75 and were followed for three to 17 years.
Job types were separated into four categories using a model that measured two variables: psychological demand and control. Job demand accounts for psychological stressors such as deadlines, workplace conflicts, and mental load or concentration. It does not account for the amount of physical labor performed or the total number of hours worked, however. Control accounts for employees’ ability to solve problems, learn new skills, and make authoritative decisions that affect their work or workplace. Based on these variables, jobs were then classified as low strain (low demand and high control), passive (low demand and low control), high strain (high demand and low control), or active (high demand and high control).
Passive jobs include janitors, miners, and other manual laborers; low strain jobs include natural scientists and architects; high strain jobs include service industry occupations like servers and nurses aids; and active jobs include doctors, teachers, and engineers.
High Demand, Low Control Jobs Increase Stroke Risk
The researchers found that people with high strain jobs had a 22 percent higher risk of stroke than those with low strain jobs. Having a passive or active job was not associated with stroke risk, they said.
In a smaller analysis including five studies with data for 126,459 women and three studies with data for 12,323 men, stroke risk was found to be significant for women—33 percent higher for those with high strain jobs than those with low strain jobs—but not for men, possibly because there were fewer studies with male participants, the researchers said.
And in another analysis that looked at three studies of ischemic stroke in 76,000 participants and two studies of hemorrhagic stroke (caused by a burst blood vessel that bleeds into the brain) in 54,495 participants, high strain jobs significantly increased the risk for ischemic stroke—by 58 percent—but not hemorrhagic stroke.
Stressful Job/Stroke Link Is Unclear
“It’s possible that high stress jobs lead to more unhealthy behaviors, such as poor eating habits, smoking, and a lack of exercise,” said study author Dingli Xu, MD, a researcher in the department of cardiology at Southern Medical University in Guangzhou, China, in a news release.
Work stress has also been shown in past research to increase the risk for heart disease, which is a risk factor for stroke, noted Jennifer J. Majersik, MD, an associate professor of medicine at the University of Utah in Salt Lake City, in an accompanying editorial. High stress jobs may also directly affect the brain, for example by promoting inflammation or over-stimulating the sympathetic nervous system, she said.
Reduce Stress, Reduce Risk
The study results suggest that giving employees more control on the job might help reduce their risk of stroke, said Dr. Majersik. Also, making sure they have access to psychological resources or therapy and allowing for more flexible work arrangements like telecommuting might help, she and the study authors said.
Staying healthy is also crucial, they emphasized. Here are three habits you can adopt right away:
· Cut Back on Salt, Fat, and Sugar. Choose fruits, vegetables, whole grains, and lean protein over processed foods.
· Raise Your Heart Rate. Aim to exercise for at least 30 minutes four times a week. Choose an activity you enjoy that gets your heart rate up, such as jogging, brisk walking, cycling, or swimming.
· Kick Butts. Smoking dramatically increases your risk of stroke, not to mention a heap of other health problems. For tips and resources to help you quit, visit smokefree.gov.
To learn more about stroke, read The Basics and browse our archive of articles on stroke. For stress-reduction tips that can help protect your brain, read “Calm Your Mind.”
Image via John Bastoen on Flickr.