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Friday, March 06, 2015
BY REBECCA HISCOTT
A simple skin biopsy could help detect Alzheimer’s and Parkinson’s disease earlier than current tools allow, according to a new study that will be presented at the American Academy of Neurology’s annual meeting in Washington, DC, in April. The study found that certain abnormal proteins appear in elevated levels in skin samples of people affected with these conditions, but not in samples from healthy individuals.
Currently, a diagnosis of Alzheimer’s or Parkinson’s cannot be made without a brain biopsy, an invasive procedure performed much later in the course of the disease, said study author Ildefonso Rodriguez-Leyva, MD, a researcher at Central Hospital at the University of San Luis Potosi in Mexico, in a news release. “This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on.”
Testing for Toxic Proteins
For the study, researchers gathered skin biopsies from 20 people with Alzheimer’s, 16 with Parkinson’s disease, and 17 with age-related dementia, and compared them with samples from 12 healthy people in the same age group.
They were looking for elevated levels of two proteins: tau, which forms “tangles” in the brains of people with Alzheimer’s, Parkinson’s, and other neurodegenerative conditions, and alpha-synuclein, which forms toxic clumps in the brains of people with Parkinson’s, blocking normal nerve function. Both of these proteins are present in healthy brains, too, but they behave abnormally and appear in excess in people with these conditions.
Since skin and brain tissue develop together in the ectoderm, the exterior layer of the human embryo, the researchers thought it might be possible to detect these abnormal proteins in the skin of Alzheimer’s and Parkinson’s patients.
Indeed, they found that people with Alzheimer’s and Parkinson’s had sevenfold higher levels of the tau protein in their skin samples compared with healthy individuals and those with age-related dementia. Those with Parkinson’s also had eightfold higher levels of alpha-synuclein.
Right now, it is unclear whether people who have not yet been diagnosed with these conditions would show the same elevated protein levels; future research will be needed to determine this, Dr. Rodriguez-Leyva said.
The Promise of Skin Testing
Diagnosing Alzheimer’s and other neurodegenerative diseases early on is believed to be crucial; earlier treatment may help keep brain tissue from degenerating further. But research has shown that the harmful proteins associated with Alzheimer’s begin to accumulate in the brain as much as two decades before the first symptoms appear; a recent study even showed that another protein linked to Alzheimer’s disease, amyloid-beta, can be found in the brains of people as young as 20 years old.
While the current findings will need to be confirmed in larger studies, Dr. Rodriguez said it was “exciting” that “we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases.” And in the future, skin tests could potentially be used to study and diagnose other neurodegenerative diseases beyond Alzheimer’s and Parkinson’s.
To learn more about Alzheimer’s disease, see Alzheimer’s Disease: The Basics and browse our archives here. For more information about Parkinson’s disease, see Parkinson’s Disease: The Basics and check out our past coverage.
Image via Ann Gordon on Flickr.
Wednesday, March 04, 2015
BY REBECCA HISCOTT
Plaques and tangles (shown in the blue-shaded areas) tend to spread through the brain in a predictable pattern as Alzheimer's disease progresses. Image via the Alzheimer’s Association.
Researchers have discovered that amyloid-beta, a protein believed to accumulate in the brains of people with Alzheimer’s, forming the toxic “plaques” that are characteristic of the disease, may appear in certain brain cells early in life—possibly as early as age 20.
The finding is “unprecedented,” said lead investigator Changiz Geula, PhD, a research professor at the Cognitive Neurology and Alzheimer’s Disease Center of the Northwestern University Feinberg School of Medicine, in a news release.
Although it was previously known that the hallmark plaques of Alzheimer’s disease (AD) can begin to accumulate as much as 20 years before symptoms occur, most people only develop Alzheimer’s after age 70, so the researchers didn’t expect to find the protein in young brain cells. “This is very significant,” Dr. Geula said. “We know that amyloid, when present for long periods of time, is bad for you.”
What the Researchers Found
For the study, which was published in the journal Brain, Northwestern researchers looked at a group of cells called basal forebrain cholinergic neurons in brain samples from three groups of deceased people: 13 people aged 20 to 66 who were cognitively normal when they died, 16 people aged 70 to 99 who were free from dementia (including two who were considered “SuperAged,” meaning they performed as well as 50- to 65-year-olds on memory tests), and 21 people aged 60 to 95 who had Alzheimer’s.
Basal forebrain cholinergic neurons are known to be closely involved in memory and attention, and are among the first brain cells to die in AD. They also commonly degenerate in normal aging, albeit at a slower rate. For this reason, these neurons are believed to be especially vulnerable to the brain changes that lead to Alzheimer’s.
The investigators found that amyloid began accumulating in these neurons very early on—even in the youngest deceased patient, who was 20 years old at the time of death. They saw greater quantities of the protein in older brains and in the brains of those with AD, suggesting ongoing amyloid build-up with age.
In these vulnerable brain cells, the protein begins to form toxic clumps, known as amyloid oligomers, in younger and older individuals alike. “This points to why these neurons die early,” Dr. Guela said. “The lifelong accumulation of amyloid in these neurons” likely makes these cells more vulnerable to breaking down in normal aging and in AD.
Nerve cells in other parts of the brain did not show the same extent of accumulation, the researchers said.
How Amyloid Kills Brain Cells
The growing clumps of amyloid “likely damage and eventually kill the neurons,” Dr. Geula explained. “It’s known that when neurons are exposed to these clumps, they trigger an excess of calcium leaking into the cell, which can cause their death.” It’s also possible that when the clumps get too big, the brain can no longer clear them away, causing them to clog the cells. The clumps may also leak amyloid outside of the brain cells, leading to the buildup of the toxic plaques that are considered a hallmark of Alzheimer’s.
The next step will be to investigate how amyloid inside these cells contributes to the overall damage seen in AD, Dr. Geula said.
Amyloid Doesn’t Guarantee Alzheimer’s
The presence of amyloid in brain cells at a young age doesn’t necessarily mean that person will go on to develop AD. According to the study authors, it appears that some small amount of amyloid is normally present in healthy cells in this region of the brain. But over time, if the brain does not clear out excess amyloid efficiently, the protein may begin to accumulate and form those toxic clumps and plaques in and around the brain cells.
Other factors also play a role in Alzheimer’s, experts say. Studies have shown that some people who have large amounts of amyloid in the brain never develop AD, for instance, while others who don’t have large amounts of amyloid still develop the condition. Studies are underway to explore the other causes and factors that contribute to this devastating disease.
Read the Neurology Now article “Treat Alzheimer’s Early” to learn more about one such study, which is currently recruiting.
To learn more about Alzheimer’s disease, consult Alzheimer’s: The Basics and browse our archives here.
Tuesday, March 03, 2015
BY REBECCA HISCOTT
Implanted RNS neurostimulator. Image copyright owned by NeuroPace, Inc.
At least 30 percent of adults with partial-onset seizures, also called focal seizures, are not able to control the condition with anti-epileptic medication, or have serious medication-related side effects, according to a 2012 Institute of Medicine report. But soon those people may have another option: a high-tech device called a responsive neurostimulator.
Results from an ongoing study published in the journal Neurology suggest that the device can reduce seizure frequency and improve quality of life over the long-term in people with poorly controlled focal seizures. It could spell relief for thousands of people with epilepsy, many of whom also experience depression and anxiety and are less able to participate in daily activities.
At the moment, there are three US Food and Drug Administration (FDA)-approved non-drug treatments for partial onset seizures: vagus nerve stimulation, which involves implanting electrodes into the brain to stimulate the vagus nerve; surgery to remove the area of the brain that generates seizures; and deep brain stimulation, in which a “brain pacemaker” sends electrical pulses to the brain nucleus. But not all patients fit the criteria to receive these treatments, and some who get the surgery or other forms of brain stimulation still experience debilitating seizures.
The New Device
The Responsive Neurostimulation (RNS) System, manufactured by NeuroPace, is implanted in the scalp, where it detects specific electrical seizure patterns pre-programmed by a physician based on electrocorticographic (ECG) measurements of a patient’s seizure activity. When it detects seizure activity, electrodes deliver brief pulses of stimulation to the seizure-generating part of the brain. The device is FDA-approved for adults with focal seizures who have failed to get their epilepsy under control with at least two antiseizure medications, and whose seizures can be shown through diagnostic testing to be generated in only one or two areas of the brain (known as epileptogenic foci).
Study Details: Responsive Neurostimulation by the Numbers
A total of 256 people over age 18 with partial seizures who fit the FDA criteria for responsive neurostimulation were implanted with the device; 230 were enrolled in the ongoing study.
On average, people with the implant had a 44 percent reduction in seizure frequency after one year and a 53 percent reduction at two years. The improvement in seizure frequency ranged from 48 percent to 66 percent in years three through six, with a 60 percent average reduction in seizures at the beginning of year three and a 66 percent reduction at the beginning of year six, suggesting that the device works in the long term, the researchers said.
Looking at the most recent three months of data available for each study participant, they reported that 84 percent of participants saw some improvement in seizure frequency, 60 percent had seizure reduction of 50 percent or more, and 16 percent of participants were seizure-free.
More than one-third of the participants experienced at least one seizure-free period of three months or longer, 23 percent had at least one seizure-free period of six months or longer, and 12.9 percent had a seizure-free period of one year or longer. However, no participants were seizure-free for the duration of the study.
An Emotional Bonus
Study participants also periodically filled out a quality of life questionnaire that asked about their emotional well-being, perceived level of social support, feelings of social isolation, energy and fatigue, and more. Not surprisingly, the questionnaires revealed that having fewer seizures was linked to improvements in anxiety, stress, and depression, as well as feelings of being more in control of their condition.
While it’s too early to start using the device outside of clinical trials, the researchers believe this promising technology offers a much-needed option for people who haven’t been served by existing epilepsy treatments.
To learn more about neurostimulation for epilepsy, browse our archives here.
Friday, February 27, 2015
BY REBECCA HISCOTT
People with attention deficit hyperactivity disorder (ADHD) are at a higher risk of dying young than those without ADHD, according to a new study published in The Lancet. Women and those who are diagnosed later in life, as well as those who have concurrent substance abuse or behavioral problems are at the greatest risk, the researchers found.
Possible Reasons for the Higher Risk
The reasons for the increased risk aren’t entirely clear, but the researchers posited some theories. For starters, people with ADHD have higher rates of behavioral and substance abuse problems, which can lead to violent and criminal behavior.
Research also shows that traits associated with ADHD such as inattention and impulsivity are linked to higher rates of accidents. Past studies indicate, for example, that people with ADHD are at a slightly higher risk of being in car accidents and having mild traumatic brain injury, and are more likely to engage in risky behaviors, said Stephen V. Faraone, PhD, a professor of psychiatry and behavioral sciences and neuroscience and physiology at SUNY Upstate Medical University in Syracuse, NY, in an editorial accompanying the study. People with ADHD may even be at a higher risk for natural causes of death, like heart attacks, since some research finds that they are more likely to be obese.
People who are diagnosed later in life may have a more severe form of the disorder, and may have gone many years without getting it under control, the study authors added; if they also have untreated behavioral or substance abuse problems, they may be more likely to engage in risky behaviors.
Women may be more at risk than men because they are less likely to be diagnosed with ADHD, Dr. Faraone said.
What the Study Found
The researchers looked at a database of 1.9 million people born in Denmark between 1981 and 2011. Among them, 32,061 people received a diagnosis of ADHD, and 107 of them died before age 31—double the rate of premature death compared to those without the disorder, even when other factors known to affect the risk of early death like age, sex, family history of psychiatric disorders, and parental age and education were taken into account.
Of the 107 people with ADHD who died over the course of the study, cause of death was available for 79 of them; 54 were found to have died from unnatural causes, like car crashes, and 42 (or 78 percent) of those unnatural premature deaths were from accidents.
Factors that Confer More Risk
People who were diagnosed with ADHD after age 18 were more than four times as likely to die early as those without ADHD, while children who were diagnosed before age six were only around twice as likely to die prematurely, the researchers found. Women and girls were at a higher relative risk of dying young than boys and men.
In addition, people with ADHD who had a co-occurring behavioral disorder or substance abuse problem—which are more common in people with ADHD than in those without the condition, studies show—were at a higher risk of early death. For instance, those who had a combination of oppositional defiant disorder (disobedience toward authority figures), conduct disorder (antisocial behavior, marked by persistent violation of social norms and the rights of others), and substance abuse problems were eight times as likely to die early.
The overall risk of premature death in children and young adults with ADHD is still quite low, the authors point out—but the results emphasize the importance of diagnosing and treating ADHD early and appropriately.
Parents and patients “can seek solace in the knowledge that the absolute risk for premature death is low, and that it and other risks can be greatly reduced with evidence-based treatments [such as medication and behavior modification],” Dr. Faraone said.
To learn more about ADHD, visit the American Academy of Neurology’s resource page and browse our archives here.
Image via Amen Clincs on Flickr.
Thursday, February 26, 2015
BY REBECCA HISCOTT
There may be a sweet spot for sleep when it comes to lowering your risk of stroke, according a new study published in the journal Neurology. That amount appears to be between six and eight hours. If you’re over age 63 and regularly sleep more than eight hours a night or younger than 60 and sleep less than six, you may be at a higher risk for stroke, according to the study.
The Long and Short of Sleep
Researchers from the University of Cambridge in the United Kingdom studied 9,692 people between the ages of 42 and 81 who had never had a stroke. The participants filled out questionnaires about their sleeping habits at the beginning of the study and again four years later, and were followed for an average of nine and a half years. During that period, 346 people had a stroke; of 986 people who reported sleeping more than eight hours a night, 52 had a stroke, and of 6,684 people who reported sleeping between six and eight hours a night, 211 had a stroke.
Overall, long sleepers were 46 percent more likely to have a stroke than average sleepers, and short sleepers were 18 percent more likely to have a stroke; however, the 18 percent figure was not mathematically significant, the researchers said.
Those who progressed from sleeping less than six hours a night to sleeping more than eight over the course of the study were at the highest risk—they were nearly four times more likely to have a stroke than average sleepers.
The Stroke-Sleep Connection
The negative effects of getting too little sleep are fairly well understood. People who regularly sleep less seven or eight hours a night are at a higher risk of obesity, diabetes, heart disease, and high blood pressure—all stroke risk factors in their own right.
But how longer sleep duration relates to stroke is less clear. “We don’t know yet whether long sleep is a cause, consequence, or early marker of ill health,” said study author Yue Leng, MPhil, a PhD student at the University of Cambridge, in a news release. “More research is needed to understand the relationship between long sleep and stroke.
Too Much Sleep May Be a Red Flag
It’s possible that sleeping more than eight hours is a sign of an underlying illness that leads to stroke, rather than a cause of stroke itself, said Alberto R. Ramos, MD, MSPH, a researcher with the University of Miami Miller School of Medicine, and James E. Gangwisch, PhD, an assistant professor in the Columbia University College of Physicians and Surgeons Department of Psychiatry, in an accompanying editorial.
For instance, too much sleep has been shown to be linked to higher rates of high blood pressure and atrial fibrillation (a form of irregular heartbeat), as well as inflammation, hardening of the arteries, and thickening of the walls of the heart, which are known risk factors for stroke and other cardiovascular problems. Sleeping too much could also be a sign of sleep apnea, a condition that raises the risk for stroke, they said. And a marked change in sleeping habits (like going from sleeping less than six hours a night to more than eight) may be an early sign of a new health problem that needs to be checked out.
If you’ve noticed a drastic change in your sleeping habits, see your doctor to look for underlying causes and discuss good sleep hygiene.
4 Ways to Reduce Your Stroke Risk
Research has shown that adopting heart-healthy habits can significantly lower your risk for stroke. Talk to your doctor about these stroke-savvy strategies:
· Improve Your Diet. Conditions like obesity, high blood pressure, and high cholesterol, all of which can result from a poor diet, can up your stroke risk. Avoid processed foods, which are loaded with added salt and sugar, moderate your alcohol intake, and fill your plate with fruits, vegetables, whole grains, and lean protein.
· Break a Sweat. Increase your activity level with moderate aerobic exercise such as walking, swimming, or cycling for 30 minutes each day. You’ll get fit and help insulate your brain against stroke, as well as Alzheimer’s and dementia.
· Kick the Habit. If the fact that smoking thins your brain hasn’t already convinced you to quit, take note: Studies have shown that smoking is the most significant lifestyle factor linked to stroke risk. Visit smokefree.gov for tips and strategies to help you quit.
· Protect Your Health. You can reduce your stroke risk by getting any existing medical conditions under control. If, for example, you have high blood pressure, atrial fibrillation, or sickle cell anemia, make sure you’re taking the right medications and adopting healthy lifestyle habits that can help treat your condition.
Look for an upcoming Q&A with experts in The Waiting Room in the April/May 2015 issue of Neurology Now to learn more about the relationship between sleep and neurologic conditions. To learn more about the link between sleep and stroke, browse our archives here.
Image via geir tønnessen on Flickr