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Monday, May 16, 2016

BY SARAH OWENS

Pimavanserin (Nuplazid), a drug used to treat symptoms of psychosis related to Parkinson's disease, has just been approved by the US Food and Drug Administration (FDA).

Citing results from a phase 3 drug trial that showed a marked reduction in hallucinations, delusions, and behavior changes in those who took pimavanserin for six weeks, the FDA granted the new antipsychotic a breakthrough therapy designation. The designation is part of a program designed to speed the development and review of drugs for serious conditions, based on preliminary evidence that the drug is substantially better than available therapies. In addition to its effectiveness, pimavanserin did not worsen motor symptoms, including shaking and tremor.

A Different Mechanism

Most traditional antipsychotics block dopamine, a neurotransmitter that regulates movement and is in short supply in people with Parkinson's disease. When dopamine is blocked, motor symptoms such as tremors and rigidity worsen. Pimavanserin, on the other hand, targets the serotonin receptor, says Michael S. Okun, MD, FAAN, Adelaide Lackner professor and chairman of neurology at the University of Florida and national medical director of the National Parkinson Foundation. "Since pimavanserin uses a serotonin pathway, it does not have the associated side effects of a typical dopamine-blocking drug."

A New Option

The new drug provides another option for people with Parkinson's disease-related psychosis who have been unable to take other antipsychotic medications to control their symptoms. "The big need for the Parkinson's disease community has been to develop a drug that controls hallucinations but does not worsen the motor symptoms," says Dr. Okun. "Pimavanserin may potentially fill that need for select patients." Side effects are considered mild to moderate and not significant and included urinary tract infections and falls.

Incidence of Psychosis

As many as 50 percent of people with Parkinson's disease experience symptoms of psychosis—seeing or hearing things that aren't there (hallucinations) and/or having false beliefs (delusions)—at some point during the course of their illness, according to the FDA. Eventually, these symptoms can become so severe that people with the disease can't "relate to loved ones or take appropriate care of themselves," according to the FDA's press release.

For more about hallucinations associated with Parkinson's disease, as well as other tips to manage psychotic behavior, visit bit.ly/HelpforHallucinations​.


Wednesday, May 11, 2016

TBI and MCI.jpeg

BY FRAN KRITZ

Research suggests that traumatic brain injury (TBI) may be a risk factor for later development of neurodegenerative diseases such as Alzheimer's disease. Now a new study finds that traumatic brain injury with a loss of consciousness for more than five minutes may put people at risk for mild cognitive impairment (MCI.) In addition, the researchers reported that people with TBI showed signs of MCI two years earlier than people who developed MCI but did not have a TBI. The findings were published in March in the Journal of Alzheimer's Disease.

Study Parameters

Researchers, led by C. Munro Cullum, PhD, a professor of psychiatry, neurology and aerotherapeutics, and neurological surgery at University of Texas Southwestern in Dallas, culled information from the National Alzheimer's Coordinating Center (NACC) database, comprising data on people with normal cognition (healthy controls) and those with dementia, to compare the cases of 3,187 people diagnosed with MCI with those of 3,244 people with normal cognition. All participants were 50 years or older. "We needed to look at frequency of TBI in controls as well as MCI," explains Dr. Cullum.

Study Results

The researchers found several factors associated with a higher risk of MCI, including TBI with loss of consciousness for more than five minutes, certain genetic risk factors, and a history of depression. TBI patients who lost consciousness were 1.2 to 1.3 times more likely to be diagnosed with MCI than those who had not had a brain injury.

Need to Identify Risk Factors

"We cannot yet determine who is at greatest risk for later-life cognitive decline following TBI, but these results suggest that a relationship exists for some people," says Dr. Cullum. "Our ultimate goal is to identify various risk factors that may play a role." The findings are "a call to arms to obtain more detailed histories on TBI," he adds. For example, the NACC database included only a few questions on concussions, he says. More information on prior concussions might help researchers determine links and potential treatments.

Potential Future Treatments for TBI

"TBI is hypothesized to activate a neurodegenerative process that may interact with age and other factors over time," says Dr. Cullum. "This study shows a correlation between TBI and MCI, but more research remains to be done to explore this apparent link. Factors such as neuroinflammation and buildup in the brain of proteins such as tau and amyloid following injury and over a person's lifetime may play a role." As treatments for amyloid and tau are developed, they might be prescribed earlier for someone who had a TBI and is thought to be at greater risk for cognitive decline later in life, Dr. Cullum says.


Tuesday, May 3, 2016

Computer post.jpg 

BY FRAN KRITZ

The early stages of cognitive decline can be hard to diagnose because symptoms such as forgetfulness or mild confusion are often attributed to medication, illness, or fatigue. Yet early diagnosis might allow patients and their families time to plan for the future. And some interventions such as medication, increased social interaction, and activities that stimulate the brain may possibly slow down or temporarily stabilize the decline. A recent small study, published online in early March 2016 in the Journal of Alzheimer's Disease, suggests another sign of cognitive decline: less time spent using a computer.

Study Parameters

Researchers at the Oregon Health and Science University (OHSU) published a small, one-month study that tracked computer use among 27 people in Portland, OR, ages 70 to 97, none of whom had signs of cognitive decline when they were enrolled. The researchers attached sensors to each participant's computer mouse to track computer use 24 hours a day one month. The amount of time spent each day in front of the computer ranged from none at all to nearly 189 minutes a day; average use was 51 minutes. After two weeks, a brain magnetic resonance image (MRI) was taken for each participant.

Brain Imaging Results

The researchers found that the participants who spent more time in front of a computer during the study had a relatively larger hippocampus and medial temporal lobe (areas of the brain responsible for memory) than the others. Signs of shrinkage in those areas have been linked to dementia and can be an early sign of Alzheimer's disease. The study participants who had higher rates of computer use also performed better on memory tests than the less active computer users.

The MRI scans did not show a difference in the relative size of the frontal lobe (the area responsible for executive function), which the lead study author Lisa Silbert, MD, an associate professor of neurology at OHSU, says was a surprise. "I was expecting computer use to be associated more with frontal executive function, which involves multitasking and planning. I wasn't expecting it to be more clearly associated with memory," she says. "Computer use could be a sensitive marker of someone at risk."

More Studies Needed

Dr. Silbert says larger and longer studies need to be conducted in order to determine whether decreased computer use could be an actual marker of cognitive decline. She and her colleagues plan to follow these and future participants for years to assess the potential association between decreased computer use and cognitive decline. "For now," says Dr. Silbert, "any decreased computer use could be an indication to start asking some questions about possible cognitive decline in order to bring a fuller picture to a physician."

Can Computer Use Help Reverse Cognitive Decline?

The study raises the question of whether using a computer can stave off or even reverse cognitive decline, but Dr. Silbert says a completely different study would be needed to determine that. "But it does raise the possibility and is something that should be studied in the future." 


Tuesday, April 26, 2016

Brain bee.jpeg 

Courtesy of the Laboratory of Neuro Imaging at UCLA and Martinos Center for Biomedical Imaging at MGH, Consortium of the Human Connectome Project


BY SARAH OWENS

Fifty six high school brain enthusiasts gathered in Washington, DC, last month to compete in the 17th Annual USA Brain Bee, and one--Karina Bao, a junior at Little Rock Central High School in Little Rock, AK—emerged victorious.

Battle of the Brains

Designed to test the knowledge of budding neuroscientists, the competition poses challenges across a range of neuroscience topics, from emotions, memory, and sleep to Alzheimer's disease, Parkinson's disease, autism, and research. Contestants have to complete a neuroanatomy laboratory practical exam with real human brains, make a diagnosis after face-to-face interactions with patient actors, analyze an MRI brain scan, and study brain tissue under a microscope. The competition culminates in a final question-and-answer session.

As champion, Bao secured a summer internship at a neuroscience lab and took home two trophies, one for her and one for her school. She also advances to the 17th World Brain Bee Championship, which will be hosted in July by the Federation of European Neuroscience Societies and held in Copenhagen, Denmark. Bao will compete against about 25 other national champions from Australia, Brazil, Canada, China, Nigeria, Poland, Turkey, the United Arab Emirates, and other countries.

Building "Better Brains"

The USA Brain Bee was established 17 years ago by Norbert Myslinski, PhD, a neuroscientist at the University of Maryland School of Dentistry to promote interest in neuroscience topics among young scholars. "I want to motivate young men and women to learn about the brain, and inspire them to consider careers in basic and clinical neurosciences," says Dr. Myslinski. The Brain Bee "builds better brains to fight brain disorders," he says. The competition has since expanded to 160 chapters in 40 regions on six continents.

For more information about the USA Brain Bee, contact Norbert Myslinski at nmyslinski@umaryland.edu or karobinson@umaryland.edu.

Read our story about last year's winner here.​


Tuesday, April 12, 2016

Parkison's psychosis.jpeg

BY FRAN KRITZ

Almost half of all Parkinson's patients experience psychosis—seeing, hearing, or smelling things that aren't there, becoming paranoid, or believing things that aren't real—at some point during their illness, usually in advanced stages. The treatment, in many instances, is antipsychotic medication, but a new study, published last month in JAMA Neurology, raises questions about their use.

Disturbing Trend

Researchers, led by Daniel Weintraub, MD, a psychiatrist and professor of neurology and psychiatry at the University of Pennsylvania School of Medicine, looked at records from a large Veterans Affairs database and compared close to 8,000 Parkinson's patients who took antipsychotic drugs at any point between 1999 and 2010 to a control group with the same number of Parkinson's disease patients who did not take antipsychotic drugs.

Each patient in the group who received the medications was compared with a control patient of the same age, gender, race, and years since diagnosis, and dementia diagnosis. The researchers found that those who took antipsychotic drugs were more than twice as likely to die during the six months after starting the drugs as those who were not given antipsychotics.

Black Box Warning

This isn't the first time a concern has been raised about an increased risk of death with antipsychotic drugs. The US Food and Drug Administration (FDA) requires "black box" warnings on antipsychotic drug labels about an increased risk of death when taken by patients with dementia. Dementia is ultimately diagnosed in about 80 percent of Parkinson's patients but a 2011 study by Dr. Weintraub published in JAMA Neurology found that the warnings had not reduced antipsychotic prescriptions for those patients.

Older Drugs Result in More Deaths

The risk of death for patients differed depending on which antipsychotic was prescribed. Older antipsychotics such as haloperidol, were found to have a 50 percent greater chance of death than newer antipsychotics, such as quetiapine, a commonly prescribed drug. The researchers don't know why older drugs cause more deaths, but a follow-up study will look at factors such as diagnoses of other diseases and injuries to see what might be causing the higher rate of deaths.  

Alternatives to Antipsychotics

Physicians should look for other ways to treat psychosis before prescribing medication, advises Dr. Weintraub. He suggests ruling out other medical conditions, reducing dopamine doses, and recommending behavioral therapy methods. "Antipsychotics should be used in these patients only when the psychosis is clinically significant, and patients probably should not be left on these drugs long-term without re-evaluation," he says.

"This study will codify what is best medical practice for the treatment of Parkinson's," says Paul Fishman, MD, PHD, a professor of neurology at the University of Maryland School of Medicine. "If doctors use them, they should use them with care."

Fishman says neurologists are hopeful about pimavanserin (Nuplazid), a new antipsychotic medication that was recommended for approval by an FDA advisory committee and could be approved later this spring. "But the cost of pimavanserin will be higher, and it will be a while before we know whether it increases the risk of death in patients," says Dr. Fishman.

For more about psychosis and Parkinson's disease, read Help with Hallucinations in the April/May 2016 issue. For more about treating psychosis, visit our archives.