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Physicians UpdateWINTER 2014

MARKETING DIRECTOR Pattie Cuen

MANAGER, MARKETING

COMMUNICATIONS Judi Goodfriend

EDITOR David Greenwald

CONTRIBUTORS Kimberly Enard Dan Gordon

MEDICAL EDITORS David T. Feinberg, md, mba Patricia Kapur, md

DESIGN Donenfeld & Associates

Copyright © 2014 by UCLA Health. All rights reserved.

For inquiries about UCLA Physicians Update, contact UCLA Health Marketing Communications, Box 956923, Los Angeles, CA 90095-6923 uclahealth.org

Physicians Update

continued on p. 4

PSYCHIATRY

New Approaches to Improve Schizophrenia Symptoms

New strategies to improve the lives of people with schizophrenia are beginning to emerge, from improved medications to effective cognitive-training programs. “This is a very exciting period in the development of treatments for schizophrenia,” says UCLA psychiatrist Stephen Marder, MD. “There are already some new approaches offering benefits out there, with a very strong possibility of other treatments becoming available very soon.”

Dr. Marder notes that it is important for physicians to recognize that the apathy and lack of motivation and social interest shown by people with schizophrenia is not laziness but part of the illness, and that these new approaches may help them. The same is true for the cognitive deficits, such as impaired attention, memory and decision-making capabilities.

WINTER 2014Psychiatry Issue

Schizophrenia p. 1

Autism p. 3

FOCUS Project p. 6

Alzheimer’s Disease p. 8

Depression p. 10

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UCLA Clinical Updates Learn about the Latest Advances from UCLA

UCLA is among the first medical centers in the region — and the only one in West Los Angeles — to offer a new breast imaging technology that improves breast cancer detection rates compared to conventional mammography while reducing the rate of false-positive results. Called digital breast tomosynthesis, the technology is now offered at two UCLA breast imaging centers and is expected to emerge as the new standard-of-care in breast imaging.

More than 38 million U.S. women undergo mammography each year for screening or diagnostic purposes. Mammography is among the most-studied screening tools in medicine today. While mammography has been proven to save lives, the technology is imperfect. Digital breast tomosynthesis addresses some of the challenges associated with standard breast imaging and provides a more accurate assessment of breast health.

UCLAHEALTH.ORG 1-800-UCLA-MD1 (1-800-825-2631)

Tomosynthesis sets a new standard in breast imagingPatients undergoing breast tomosynthesis can be assured they are receiving the most advanced imaging technology available, says Anne Hoyt, MD, clinical professor and director of the Barbara Kort Women’s Imaging Center. Radiation exposure using the new Hologic C-View technology is similar to conventional mammography, and patients are likely to experience fewer call-backs for a second scan.

“Overlapping dense tissue gives the illusion that there is something there,” Dr. Hoyt explains. “Sometimes women are scheduled to come back, and it turns out there is nothing there. These call-backs create a lot of anxiety among women. This is one of the criticisms of mammography.”

At UCLA, breast tomosynthesis is used in both screening and diagnostic settings. While breast tomosynthesis can benefit all patients, women with dense breast tissue may be the best candidates for the technology. “The number-one reason for false-negative mammograms is dense breast tissue,” Dr. Hoyt says.

Digital breast tomosynthesis marks a new era in breast imaging

The 3-D digital tomosynthesis image (right) reveals the spiculated (sunburst) margin of the central mass, suggesting that it is cancerous. In the conventional 2-D image (left), the same mass is partially hidden by overlapping normal breast tissue and the diagnostically significant spiculated margin is easily missed.

Over the past 15 years, children and adolescents with severe irritability and aggressive outbursts have received increased attention from medical professionals as more and more of these youths have been diagnosed with pediatric bipolar disorder. In some cases, the pediatric patients clearly meet current diagnostic criteria for bipolar disorder, but in others, the diagnosis is unclear. Without validated biomarkers to diagnose bipolar disorder, this rising trend — with some data suggesting it may have increased by as much as 400 percent from 1994 to 2003 — has become one of the greatest controversies in child and adolescent psychiatry.

A growing number of researchers, however, believe that many of these pediatric patients may have a different disorder, which they have termed Severe Mood Dysregulation (SMD). With SMD a youth will exhibit outbursts that go far beyond a typical temper tantrum and require clinical intervention, but they will not experience other symptoms such as the manic and prolonged euphoria that often presents with bipolar disorder.

SMD is not an official diagnosis, but new research is under way to determine whether it should be considered a psychiatric disorder, which could ultimately affect how children with chronic and severe irritability are diagnosed and subsequently treated. A new UCLA research study at the Semel Institute for Neuroscience and Human Behavior seeks to develop a better characterization of SMD. The UCLA study is one of the first to be conducted outside of the National Institute of Mental Health.


A new diagnosis could lead to better treatmentPhysicians are concerned that a growing number of children and adolescents currently being diagnosed with bipolar disorder could receive more appropriate care if Severe Mood Dysregulation (SMD) were an officially recognized diagnosis. With a separate diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, these young patient could be treated with different medications than those used for bipolar disorder, sparing them the risk of side effects from the powerful drugs used to treat that condition. In addition, an SMD diagnosis could carry less social stigma than a diagnosis of bipolar disorder.

“We don’t really know the population yet,” says James J. McGough, MD, professor of clinical psychiatry in the UCLA Semel Institute Division of Child & Adolescent Psychiatry and lead investigator of the study. “But proper care always begins with an accurate diagnosis. The better we understand the underlying condition, the more precise we can be in our diagnosis and the better treatment we can offer these patients to help improve their ability to function in family, social and school settings.”

UCLA study to characterize severe mood dysregulation

Neuroendocrine cancer, which is diagnosed in about 8,000 Americans each year, consists of a heterogeneous group of tumors that arise mostly in the gastrointestinal tract. These tumors are often challenging to diagnose and treat. Symptoms can be vague, consisting of diarrhea, abdominal cramps, shortness of breath, blood pressure changes, headaches and rashes. Tumors may not be detected by routine imaging. As a result, a diagnosis is often made when the disease is at an advanced stage.

Appropriate treatment of neuroendocrine tumors depends on the particular type of tumor, where it originated and its stage and grade. Recent advancements in molecular imaging with PET have led to a greater ability to accurately evaluate neuroendocrine tumors.

UCLA Nuclear Medicine, in a joint venture with UCLA Radiology, is the first facility on the West Coast to assess neuroendocrine tumors using positron emission tomography with computed tomography (PET/CT) and a new imaging agent called gallium-68 DOTATATE (68Ga DOTATATE).


Working to make DOTATATE more availableWhile neuroendocrine tumor imaging using DOTATATE PET/CT is well established in Europe, the technology is less well known in the United States and is dramatically underutilized, says Martin Allen-Auerbach, MD, medical director of the UCLA Nuclear Medicine Clinic.

“Before you decide what treatment to give patients, you need to stage and characterize the tumor,” Dr. Allen-Auerbach explains. “The image quality of the current imaging technology (octreotide SPECT) is clearly inferior to DOTATATE PET/CT. That has been proven in the scientific literature. Many studies have compared the two modalities side by side. DOTATATE PET/CT has superior sensitivity and specificity when it comes to neuroendocrine neoplasm.”

At this time, DOTATATE PET/CT isn’t routinely covered by insurance. However, the staff of the UCLA Nuclear Medicine Clinic works with each patient to assess reimbursement.

“We hope insurance reimburse-ment policies will change soon because DOTATE actually costs less than the currently covered octreotide SPECT scan,” Dr. Allen-Auerbach says.

DOTATATE PET/CT represents enhanced molecular imaging for neuroendocrine tumors

3-D PET reconstruction (left) and coronal slice of fused PET/CT image (right) showing metastatic disease in the liver (blue arrows) and the primary cancer site in the small bowel (red arrow). The site of the primary disease could not be identified prior to this scan.

Pediatric Thyroid NodulesBecause thyroid nodules in children are often too small to feel or cause symptoms, children at risk of thyroid cancer should be evaluated at a center with expertise in advanced diagnostic and treatment techniques.

Mental Illness with Co-occurring AddictionSimultaneous treatment of both mental illness and addiction can increase the chances for long-term recovery from alcoholism or drug addiction.

Reproductive MedicineObesity can have adverse effects on fertility, and women should ideally be counseled on the medical, obstetric and neonatal consequences of obesity and its longer-term implications for offspring.

Advances in growing embryos to an advanced stage of physiologic development have made single-embryo transfer a superior procedure for many patients seeking in vitro fertilization.

Geneticists at UCLA counsel patients on the use of prenatal genetic screening, and patients referred for oncofertility receive therapy that is sensitive to oncologists’ treatment plans.

Pulmonary MedicineUCLA Peninsula Pulmonary offers comprehensive pulmonary, critical care and sleep medicine services to South Bay residents.

Breast TomosynthesisUCLA is among the first medical centers in the region to offer breast tomosynthesis, a new breast imaging technology that improves breast cancer detection rates while reducing false-positive results.

Mindful AwarenessMindful awareness, a concept focusing on attention and awareness — essentially being “in the moment” — can be a strong antidote for stress, anxiety and depression, and can help alleviate chronic pain.

Pediatric Sports Concussion ClinicWhile most young athletes who suffer a concussion will recover with time and rest, some will experience unusual symptoms, delayed recovery or chronic symptoms that can best be treated in a specialized clinic.

Santa Monica Obstetrics and Gynecology UCLA Obstetrics and Gynecology, Santa Monica combines the comfort and convenience of care delivered close to home with the expertise and technological capabilities featured in major academic medical centers.

Neuroendocrine TumorsUCLA is the first facility on the West Coast to assess neuroendocrine tumors using DOTATATE PET/CT, which offers image quality that is clearly superior to standard octreotide SPECT imaging.

Severe Mood DysregulationNew research is under way to determine if severe mood dysregulation should be considered a psychiatric disorder, which could ultimately affect how children with chronic and severe irritability are diagnosed and treated.

To download these and other clinical advances at UCLA Health, go to: uclahealth.org/clinicalupdates

UCLAHEALTH.ORG 1-800-UCLA-888 (1-800-825-2888)

News from UCLA Health

Resnick Hospital Recognized for Records ManagementThe Stewart and Lynda Resnick Neuropsychiatric Hospital at UCLA is one of only two psychiatric hospitals nationwide, and the only academic psychiatric hospital, to earn HIMSS Analytics’ acute-care Stage 7 award. Achieving the award represents attainment of the highest level of electronic medical-record progress at hospitals and health systems.

uclahealth.org/Stage7Award

Disrupted Bond Impacts Child’s BrainChildren who experience profound neglect have been found to be more prone to a behavior known as “indiscriminate friendliness,” characterized by an inappropriate willingness to approach adults, including strangers.

uclahealth.org/disruptedbond

Context Counts for Anxious Children and TeensAnxiety disorders are common in children and adolescents, affecting up to 25 percent of the youth population. Anxiety causes distress and functional impairment and, if left untreated, can result in bad grades, problems at home and increased rates of psychiatric disorders in adulthood.

uclahealth.org/teenanxiety

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3 UCLA Physicians Update

Increased Autism Diagnoses Indicates Improved Standards for Recognizing Symptoms

Despite the complexities of diagnosing autism spectrum disorders (ASDs), the number of reported cases has increased by more than 20 percent in recent years, an indication that clinicians have become better at recognizing symptoms of ASDs.

“Early identif ication and intervention are critical,” says Amanda Gulsrud, PhD, clinical director of the Chi ld and Adult Neurodevelopmental (CAN) Clinic at UCLA and a co-investigator in UCLA’s Autism Center of Excellence (ACE). “As we continue to learn more about how to enhance the benefits of behavioral therapies to maximize long-term neurodevelopmental outcomes, we know that one of the most universal and best indicators is the age at which the child enters that intervention.”

Diagnosing ASD in children younger than 3 years of age is often difficult. There is no medical test, such as a blood test, to diagnose ASD. Instead, clinicians rely on behavioral observation and developmental history. The gold standard in the field is the use of the Autism Diagnostic Observation Schedule (ADOS) in conjunction with the Autism Diagnostic Interview-Revised (ADI-R) with the parent or caregiver of the affected child.

From the behavioral standpoint, clinicians look for red flags related to the way a child interacts socially with others, including the use of coordinated eye contact with another person, and the way a child gestures or points when communicating. “We see a wide range of behaviors in children with ASD, and not all treatments will work universally for all children on the spectrum,” Dr. Gulsrud says. “It is important to provide differentiated treatments for children based on their needs and individual symptoms.”

UCLA’s CAN Clinic provides multidisciplinary evaluation and individualized treatment for patients of all ages with suspected or diagnosed neurodevelopmental disorders, with a focus on ASD. Once a course of treatment is prescribed, results should be consistent and measurable, says

James McCracken, MD, medical director of the CAN Clinic and director of the Division of Child and Adolescent Psychiatry at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.

“Physicians should expect to see concrete evidence of progress in their patients with ASD every three to four months,” Dr. McCracken says. “If not, they should start to ask questions about why the prescribed therapies are not working.”

Dr. McCracken is principal investigator of a $9-million award from the National Institute of Mental Health to create and lead a network of U.S. academic centers that will carry out early “high-risk/high-reward” studies of promising new drugs that may help restore normal development and brain function in children and adults with ASDs.

“Current medical treatments for ASD help to manage difficult behaviors but do not have much impact on the core problems of ASD, despite its known genetic and biological basis,” Dr. McCracken says. “This initiative has the potential to vastly accelerate our progress in this area.”

As part of UCLA’s ACE Center, researchers are also involved in studies focused on a variety of issues related to ASD. They are investigating the genetic and biological underpinnings of ASD, working to improve clinical interventions for 12-to-21-month-old children at-risk for the disorder, using functional magnetic resonance imaging (FMRI) technology to examine infant and child brain development, striving to understand gender differences in symptom presentation and evaluating new treatments for patients with the most severe forms of ASD.

“One-in-three children affected by an ASD never develops the ability to speak in phrases,” says Dr. McCracken. “We are now conducting one of the first studies that tests medication in combination with intensive communication therapy as a way to accelerate uptake of language in these children.”

AutismNews from UCLA Health

Resnick Hospital Recognized for Records ManagementThe Stewart and Lynda Resnick Neuropsychiatric Hospital at UCLA is one of only two psychiatric hospitals nationwide, and the only academic psychiatric hospital, to earn HIMSS Analytics’ acute-care Stage 7 award. Achieving the award represents attainment of the highest level of electronic medical-record progress at hospitals and health systems.

uclahealth.org/Stage7Award

Disrupted Bond Impacts Child’s BrainChildren who experience profound neglect have been found to be more prone to a behavior known as “indiscriminate friendliness,” characterized by an inappropriate willingness to approach adults, including strangers.

uclahealth.org/disruptedbond

Context Counts for Anxious Children and TeensAnxiety disorders are common in children and adolescents, affecting up to 25 percent of the youth population. Anxiety causes distress and functional impairment and, if left untreated, can result in bad grades, problems at home and increased rates of psychiatric disorders in adulthood.

uclahealth.org/teenanxiety

Diagnosing ASD in children younger than

3 years of age is often difficult. There is

no medical test, such as a blood test,

to diagnose ASD. Instead, clinicians

rely on behavioral observation and

developmental history.

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COVER STORY


New strategies to improve the lives of

people with schizophrenia are beginning

to emerge, from improved medications to

effective cognitive-training programs.

Until recently, treatments available for

schizophrenia have been dominated by

antipsychotic drugs.

Various cognitive-training programs have

been designed to help patients improve

memory, attention and social recognition.

STORY HIGHLIGHTS


Until recently, treatments available for schizophrenia have been dominated byantipsychotic drugs. While such medications reduce the hallucinations and delusions associated with the disorder, they fail to address the major symptoms that impede the daily function of people with schizophrenia — from their school performance to their ability to thrive in the workplace.

The need for medical treatments to improve cognition and negative symptoms for people

with schizophrenia led the National Institute of Mental Health to fund a large initiative, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), based at UCLA. The initiative is headed by Dr. Marder and Michael Green, PhD. The effort focused on developing better instruments for measuring cognition and negative symptoms in clinical trials, as well as a scientific consensus on the neurobiology underlying these impairments and the most fruitful potential molecular targets for new drug compounds.

“Following MATRICS, there has been a huge interest on the part of both the pharmaceutical industry and academia in targeting these domains for schizophrenia for which there have never been effective treatments,” Dr. Marder says. Facilitated by the methods developed in the UCLA-led initiative, a number of promising drugs targeting either the cognitive or negative symptoms have moved into late-stage clinical trials and could be approved by the U.S. Food and Drug Administration sometime in 2014.

At the same time, Dr. Marder notes, there has been substantial activity in the use of various cognitive-training programs designed to help patients improve memory, attention and social cognition. “A number of studies have shown these treatments to be effective,” says Dr. Marder. Effective programs he, Dr. Green and William Horan, PhD, have studied include group-based psychosocial approaches that employ videos and other tools to assist patients in recognizing facial expressions, emotions and gestures.

In the UCLA Aftercare Research Program, an outpatient clinic of the Jane and Terry Semel Institute of Neuroscience and Human Behavior at UCLA directed by Keith Nuechterlein, PhD, which provides diagnosis and treatment services for early-phase schizophrenia patients, faculty have found that Internet-based programs that present a series of challenging mental tasks can, over time, build patients’ cognitive skills in a way that may help them at work and in social interactions.

“Cognitive skills are associated with success at work and school,” says Joseph Ventura, PhD, senior research psychologist and the program’s

(continued from cover)

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“Following MATRICS, there has been a huge interest on the part of both the pharmaceutical industry and academia in targeting these domains for schizophrenia for which there have never been effective treatments,” Dr. Marder says. Facilitated by the methods developed in the UCLA-led initiative, a number of promising drugs targeting either the cognitive or negative symptoms have moved into late-stage clinical trials and could be approved by the U.S. Food and Drug Administration sometime in 2014.

At the same time, Dr. Marder notes, there has been substantial activity in the use of various cognitive-training programs designed to help patients improve memory, attention and social cognition. “A number of studies have shown these treatments to be effective,” says Dr. Marder. Effective programs he, Dr. Green and William Horan, PhD, have studied include group-based psychosocial approaches that employ videos and other tools to assist patients in recognizing facial expressions, emotions and gestures.

In the UCLA Aftercare Research Program, an outpatient clinic of the Jane and Terry Semel Institute of Neuroscience and Human Behavior at UCLA directed by Keith Nuechterlein, PhD, which provides diagnosis and treatment services for early-phase schizophrenia patients, faculty have found that Internet-based programs that present a series of challenging mental tasks can, over time, build patients’ cognitive skills in a way that may help them at work and in social interactions.

“Cognitive skills are associated with success at work and school,” says Joseph Ventura, PhD, senior research psychologist and the program’s

director of cognitive remediation. “Most people diagnosed with schizophrenia have deficits — often substantial — in areas such as attention, focus, reasoning, problem solving and the ability to learn new information, and these can be the primary reasons they have trouble in daily living. The premise of this type of training is based on the plasticity of the brain — its ability to respond to environmental stimulators in a way that can improve neuronal connections and improve the brain’s performance.”

The group led by Drs. Nuechterlein and Ventura has studied the impact of programs that engage participants in computer-based games in which they are challenged to improve on their performance. The researchers conduct a series of cognitive tests both before and after six months of training to determine the extent to which the skills honed in the computer exercises improve overall cognition. The studies have found that participants show a moderate degree of improvement in the cognitive tasks after the six-month training. In addition, study participants showed moderate improvement in their level of engagement in workplace activities. The UCLA researchers are now seeking to determine the optimal level of training for patients, the sustainability of the effects, and how to modify programs to help participants who fail to respond to the training.

“We are very encouraged,” says Dr. Ventura. “We see this type of cognitive training as potentially being one component of a larger package of treatment for people with schizophrenia. It’s not going to replace drug treatment, case management and psychosocial support, but it can be a good complement that, in combination with these other strategies, can significantly improve these patients’ quality of life.”

Schizophrenia

The need for medical treatments to

improve cognition and negative symptoms

for people with schizophrenia led the

National Institute of Mental Health to fund

a large initiative, based at UCLA.

“ This is a very exciting period in the development of treatments for schizophrenia. There are already some new approaches offering benefits out there, with a very strong possibility of other treatments becoming available very soon.”

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In the 12 years of conflict in Iraq and Afghanistan since 9/11, tens of thousands of families have experienced a parent being deployed multiple times. Research suggests that such repeated separations amid fears about combat risk increases the likelihood of anxiety and other emotional difficulties in children, as well as contributing to psychological distress in the parent left behind. And the challenges don’t end with the return of the service member, who often struggles to reintegrate while dealing with injuries or significant combat stress reactions. In 2006, UCLA psychiatrist Patricia Lester, MD, and colleagues at UCLA and Harvard created FOCUS — Families Overcoming Under Stress — to help address the needs of these families. Since then, the UCLA-led program, of which Dr. Lester is director, has touched the lives of more than 400,000 military-family members through evidence-informed resiliency training. UCLA provides the FOCUS program to 24 military installations under contract with the U.S. Navy Bureau of Medicine and Surgery. In addition, the UCLA Nathanson Family Resilience Center provides FOCUS services to veteran

families both locally and nationally, including in partnership with UCLA’s Operation Mend.

What was the perceived need when you were approached by military mental-health professionals about creating such a program?

The military providers who were seeing these families were facing unique circumstances. For example, parents were unprepared to talk with their children about catastrophic injuries, and it was becoming apparent that the wars we were engaged in were going to mean an extended period of combat with repeated deployments. The psychological-health programming in place at that time was geared more for peacetime circumstances. There was not enough known about how to assist members of military families in coping with separations involving combat, and parents returning with post-traumatic stress and physical injuries. So with feedback from military providers and family members, we adapted resiliency-promoting interventions our group had developed and tested for families facing other types of adversity, customizing FOCUS to the specific circumstances of military families.

FOCUS was created to meet the unique

psychological health needs of military

families facing the prospect of lengthy

multiple deployments.

Since its inception, FOCUS has

touched the lives of more than 400,000

military-family members through

evidence-informed resiliency training.

Preliminary studies on the effects of

FOCUS on military families have found

improvements in family communication

and functioning, reduced anxiety and

depression in adults, and less emotional

distress in children.

STORY HIGHLIGHTS

FOCUS Attention on Emotional Needs of Military Families

Patricia Lester, MD

FOCUS Project

130250_Mag.indd 6 1/21/14 11:51 PM

Many service members struggle with mental-health problems when they return from combat. What is known about the effects on their spouses and children?

The long-term implications of repeated combat deployments on the psychological health of family members are still being studied, but a growing body of evidence suggests that up to one-third of military children show clinically significant symptoms of anxiety, and that both military children and military spouses have higher rates of referral for inpatient and outpatient mental-health treatment. These long periods of separation in the context of danger are not something you see in a civilian population. For families, this means major milestones in which the parent is not there, and a much greater level of separation anxiety among the children. For spouses who stay home, there is a higher risk of depression, child neglect and maltreatment as they juggle double parenting duties while being worried and distracted about their loved one’s safety. And when the military parent returns coping with mental-health issues, it may be difficult to fully engage in family activities, and some of these behavior changes may be confusing to a child.

What are the key components of the FOCUS program?

We use an approach called indicated prevention — preparing families to better manage the stressful times before there is a clinical need. Over the course of eight weeks, families meet with FOCUS providers. The program starts with an assessment — a resilience “check-in” using Web-based technology to screen for issues known to affect military families — to help tailor the intervention. Through education, families become more aware of the potential impact of deployment on each of them, including the effects of child separation, post-traumatic stress and traumatic brain injury. Family members make a timeline of their experience, documenting their ups and downs in a way that allows them to build on strengths and address stress. They are then taught five resilience skills: emotional regulation, communication, problem solving, goal setting and traumatic-stress-reminder management —

learning how to cope with triggers that recall separation, trauma or loss. Often, these families have never really discussed some of the difficult things they’ve been through. Learning honest and effective communication helps them to come together, address misunderstandings and have a clearer sense of their experience, which we know is an important feature of family resilience.

What is known about the efficacy of the program?

We’re in the process of a long-term study of the effects of FOCUS on military families, but preliminary work has found improvements in family communication and functioning. Benefits have included reductions in anxiety and depression in the adults, as well as less emotional distress and fewer problem behaviors in the children and improvements in their peer relationships, pro-social skills and coping.

How has FOCUS been received by the military branches?

FOCUS has been very well received. We have expanded the program so that customized versions are now offered specifically for couples, families with young children and in schools. In addition, we have adapted the program for veterans who have returned home to their communities. We are working with UCLA Operation Mend and other partners to deliver FOCUS prevention services through a range of innovative platforms: video teleconferencing, mobile applications and Web-based delivery.


FOCUS Attention on Emotional Needs of Military Families

FOCUS has been expanded to include

customized versions specifically for

couples, families with young children and

in schools, and for veterans who have

returned home to their communities.

“ With feedback from military providers and family members, we adapted resiliency-promoting interventions our group had developed and tested for families facing other types of adversity, customizing FOCUS to the specific circumstances of military families.”

For more information about FOCUS, go to: focusproject.org

130250_Mag.indd 7 1/21/14 11:51 PM

Patients at risk for Alzheimer’s disease

should be advised of the importance

of lifestyle in preventing or delaying

memory impairment.

Newer types of PET scans are focusing

on the protein deposits that build up in

the brain of Alzheimer’s patients as a

potential early indicator.

For the majority of patients, nongenetic

factors, including lifestyle choices, are

more important to their brain health.

STORY HIGHLIGHTS


Maintaining a Healthy Brain Easier than Repairing a Damaged Brain

But Dr. Small points out that for the majority of the population, nongenetic factors are more important to their brain health — and that lifestyle choices have a much greater impact than most people realize. For example, the widely cited MacArthur study on successful aging concluded that genetics accounts for approximately one-third of cognitive and physical success in aging. “That means two-thirds must be nongenetic,” says Dr. Small, who has written a number of books on the topic, most recently The Alzheimer’s Prevention Program: Keep Your Brain Healthy for the Rest of Your Life. “We are learning more and more about these nongenetic protective factors that might be under our control: nutrition, physical fitness, stress management and cognitive exercise.”

In the area of nutrition, perhaps the most important strategy involves weight management. “We know that if you’re overweight, that doubles your risk for Alzheimer’s, and if you’re obese, it quadruples your risk,” Dr. Small says. “The good news is that new studies are showing that if you reduce your weight, you can significantly improve your cognitive performance.” As for what to eat, studies suggest a diet rich in omega-3 fatty acids and low in omega-6 fatty acids is healthier for the brain. Other brain-health strategies include consuming antioxidant fruits and vegetables and minimizing refined sugars and processed foods.

Strong evidence supports the idea that physical fitness — particularly cardiovascular conditioning — can provide cognitive benefits, Dr. Small adds. “During exercise, the heart is pumping nutrients to the brain cells, and the body is producing brain-derived neurotrophic factor, which causes dendrites to sprout branches — the tentacles that connect brain cells,” he explains. Stress

As researchers continue to move toward earlier detection of Alzheimer’s disease through improved neuroimaging strategies and genetic discoveries, a UCLA Alzheimer’s and longevity expert stresses that patients should be advised of the importance of lifestyle in preventing or delaying memory impairment — even if they have yet to show any symptoms.

Although there is no cure for Alzheimer’s, finding ways to detect it at an earlier stage has significant clinical implications, says Gary Small, MD, professor of psychiatry and biobehavioral sciences in the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA and director of the UCLA Longevity Center. “If we can identify problems early, we have a better chance of protecting the brain while there are still intact brain cells,” Dr. Small explains. “It is easier to maintain a healthy brain than to repair a damaged brain.”

Through neuroimaging and genetic studies, researchers are looking for biological markers that will help to detect Alzheimer’s before major damage has occurred. Structural imaging

with MRI or CT techniques is routinely used to evaluate patients experiencing memory loss — typically to rule out possible factors such as a tumor or stroke. More revealing in early Alzheimer’s diagnosis is functional imaging with PET scans — in particular fluorodeoxyglucose (FDG) PET, which measures glucose metabolism in areas of the brain that are involved in memory, learning and problem solving.

Now, newer types of PET scans are focusing on the protein deposits that build up in the brain of Alzheimer’s patients as a potential early indicator. This includes an approach developed by Dr. Small and colleagues at UCLA. “We use chemical markers that temporarily attach themselves to the abnormal protein deposits that define the disease: amyloid and tau,” Dr. Small explains. Other approaches attach only to amyloid, he notes, and tau appears to correlate more closely with the disease. Dr. Small’s group is currently studying the approach in research protocols.

What is known about genetic factors falls into two categories. In rare cases, families have an autosomal-dominant inheritance pattern, meaning that half of the family members will get Alzheimer’s disease — typically with early onset. Individuals with such a family history should consult a genetic counselor and potentially be tested for the mutation that is causing the inherited form of the disease, Dr. Small says.

Much more common are genetic indicators that have been found to increase the risk of Alzheimer’s. The best-understood of these is the apolipoprotein E (ApoE) gene, which has three forms: 2, 3 and 4. In the general population, it is estimated that as many as one-in-five people have ApoE4, putting them at a higher risk for Alzheimer’s disease. Because the gene is neither necessary nor sufficient to cause Alzheimer’s, Dr. Small notes, it isn’t recommended as a screening tool. It is, however, useful in research. “If we find that people with mild memory loss who have ApoE4 respond better to a treatment, that is important to know,” he says.

Alzheimer’s Disease

130250_Mag.indd 8 1/21/14 11:51 PM


Maintaining a Healthy Brain Easier than Repairing a Damaged Brain

But Dr. Small points out that for the majority of the population, nongenetic factors are more important to their brain health — and that lifestyle choices have a much greater impact than most people realize. For example, the widely cited MacArthur study on successful aging concluded that genetics accounts for approximately one-third of cognitive and physical success in aging. “That means two-thirds must be nongenetic,” says Dr. Small, who has written a number of books on the topic, most recently The Alzheimer’s Prevention Program: Keep Your Brain Healthy for the Rest of Your Life. “We are learning more and more about these nongenetic protective factors that might be under our control: nutrition, physical fitness, stress management and cognitive exercise.”

In the area of nutrition, perhaps the most important strategy involves weight management. “We know that if you’re overweight, that doubles your risk for Alzheimer’s, and if you’re obese, it quadruples your risk,” Dr. Small says. “The good news is that new studies are showing that if you reduce your weight, you can significantly improve your cognitive performance.” As for what to eat, studies suggest a diet rich in omega-3 fatty acids and low in omega-6 fatty acids is healthier for the brain. Other brain-health strategies include consuming antioxidant fruits and vegetables and minimizing refined sugars and processed foods.

Strong evidence supports the idea that physical fitness — particularly cardiovascular conditioning — can provide cognitive benefits, Dr. Small adds. “During exercise, the heart is pumping nutrients to the brain cells, and the body is producing brain-derived neurotrophic factor, which causes dendrites to sprout branches — the tentacles that connect brain cells,” he explains. Stress

management is also believed to be important. Chronic stress in animals, for example, has been shown to lead to memory decline. Human studies have found that people who are prone to stress have higher rates of Alzheimer’s.

Dr. Small and others have also reported findings indicating that mental stimulation, including memory training, improves cognitive performance and may lower the Alzheimer’s risk. Based on that evidence, the UCLA Longevity Center offers memory-related classes in more than a dozen states nationwide, tailored to different populations. Brain Boot Camp, a three-hour course, teaches lifestyle strategies for promoting brain health. Memory Training is a weekly program providing practical techniques for enhancing memory ability over the course of four weeks. Memory Fitness is designed for people in senior living, while Memory Care targets people experiencing mild memory loss and their caregivers.

“There is tremendous interest in these strategies,” Dr. Small concludes. “People want to know what they can do to take care of themselves. As physicians, we should be communicating that information and emphasizing that it’s never too early to start taking proactive steps to protect the brain.”

Through neuroimaging and genetic studies, researchers are looking for biological markers that will help to detect Alzheimer’s before major damage has occurred.

(Top) Image of FDDNP PET scan (left),

MRI scan (middle) and FDG PET scan

(right) of a patient with Alzheimer’s

disease and a control subject. The FDDNP

PET provides a measure of both amyloid

plaques and tau tangles (warm colors)

in the patient with Alzheimer’s disease.

The FDG PET scan shows low metabolism

(cool colors) in those same brain areas

that control memory and thinking in the

Alzheimer’s patient.

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A major clinical trial has shown that only about one-third of adults with major depression will respond after their first medication trial, and the likelihood that similar therapies will succeed declines with each new attempt, leaving about 20-to-30 percent of patients with treatment-resistant depression (TRD). However, newer neuromodulation therapies, along with refinements in older ones that deliver electrical impulses to specific areas of the brain, can help to restore normal function and improve outcomes.

Mental disorders, including depression, affect an estimated one-in-four adults in the United States each year, and for many patients the first line of treatment is medication. But for those who are unable to tolerate the side effects from prescribed medicines or have tried without success many different drugs, so-called neuromodulation offers the hope of meaningful benefit, says Ian Cook, MD, director of the Depression Research & Clinic Program at UCLA.

“With neuromodulation, we can use noninvasive or minimally invasive techniques to change the levels of activity within targeted circuits of the brain that are important for treating illness, while providing clinically significant benefits, with fewer side effects,” Dr. Cook explains.

One of the newest neuromodulation strategies, trigeminal nerve stimulation (TNS), delivers low-energy electrical stimulation through a patch placed on the forehead to specific areas of the brain that are associated with epilepsy, depression, attention deficit hyperactivity disorder (ADHD) and post-traumatic stress (PTS). TNS was invented at UCLA, by Dr. Cook, neurologist Christopher DeGiorgio, MD, and their colleagues, for treatment of drug-resistant epilepsy, and later has been studied for treatment-resistant depression. Although it is approved in Canada and Europe for those conditions, TNS must still be evaluated in U.S. clinical trials before being considered for FDA-approval. In preliminary studies, TNS has


Neuromodulation Offers New Options for Treatment-Resistant Depression

Trigeminal nerve stimulation delivers

low-energy electrical stimulation to

specific areas of the brain associated

with epilepsy, depression, attention

deficit hyperactivity disorder and

post-traumatic stress.

Transcranial magnetic stimulation

uses magnetic energy to stimulate

parts of the brain that regulate mood.

STORY HIGHLIGHTS

Depression

130250_Mag.indd 10 1/21/14 11:52 PM

been associated with reduced seizures in patients with epilepsy and improvements in behavior and cognitive function in children with ADHD and in trauma-associated symptoms in adults with PTS.

Another approach, transcranial magnetic stimulation (TMS), uses magnetic energy to stimulate parts of the brain that regulate mood. It is currently used in one-of-two ways: by stimulating the outer layers of the brain or by targeting deeper brain structures. Dr. Cook’s program has been treating patients with an FDA-approved TMS system since 2009.

“It is hard to find a one-size-fits-all treatment with a condition like depression, so we approach it using different pathways,” Dr. Cook says. TMS is FDA-approved as a stand-alone treatment for depression that is unresponsive to medications, but in practice it is often used as a complementary treatment strategy, added on to medications or psychotherapy.

“We still have no clear idea how it all works,” says Alexander Bystritsky, MD, PhD, director of the Anxiety Disorders Program at UCLA. “We need more studies to explore TMS as a stand-alone therapy in patients without prior drug treatments and to investigate how TMS potentially interacts with prescribed medicines and therapy.”

Researchers are just beginning to understand the parameters and pathways through which TMSand other neuromodulation strategies may be used for specific psychiatric disorders, according to Dr. Bystritsky. For example, deep-brain stimulation (DBS) is a surgical procedure that involves implanting a pacemaker-like device in the chest wall and placing electrodes in the brain to send out electrical impulses to specific regions of the brain. Although DBS is commonly used to treat the symptoms of Parkinson’s disease and related neurological disorders, severe obsessive-compulsive disorder (OCD) is the only psychiatric condition for which DBS is FDA-approved (under a humanitarian-device exemption). At UCLA,researchers are conducting studies to explore the potential of DBS for treating OCD and depression and other conditions.

The researchers are also exploring noninvasive methods to stimulate deeper structures within the brain, such as deep magnetic brain stimulation (DrTMS) and low-intensity focused ultrasound pulse (LIFUP). Currently Dr. Bystritsky is

conducting a study of DrTMS in bipolar disorder.

“Bipolar disease is a tricky disorder to treat because antidepressants can trigger patients into a manic state or make them very anxious,” Dr. Bystritsky explains. “A single course of DrTMS combined with mood stabilizers may potentially be effective in quickly treating depression in bipolar patients.” The DrTMS technique was recently approved by the FDA for the treatment of unipolar depression.

In patients with hard-to-treat depression, DBS research is attempting to delineate the dysfunctional brain circuits that are most critical to alleviating depressive symptoms and to determine when DBS is indicated given the inherent risks involved.

“The surgical risks are quite low when DBS is performed by an experienced team, but there are risks associated with stimulation, such as increased anxiety, restlessness and mood changes” says Randall Espinoza, MD, MPH, director of the Electroconvulsive Therapy Program at UCLA. In current trials, DBS has been associated with a 40-to-50 percent response rate for patients who have not previously responded to other available treatments, with 30 percent of patients achieving remission of depressive symptoms and 90 percent of patients opting to continue DBS long-term, which speaks to general safety, tolerability and low occurrence of side-effects. DBS is also being studied for PTS, chronic-pain management, schizophrenia and severe OCD.

The oldest neuromodulation technique, electroconvulsive therapy (ECT), continues to be both widely used in clinical practice and investigated in research studies. “ECT is one of the most robust treatments we have for psychotic, suicidal, catatonic or medication-refractory depression, but we are investigating ways to increase the response rate and lessen associated cognitive side-effects,” Dr. Espinoza says.

He adds that an important goal of neuro-modulation research is to identify biosignatures of antidepressant response that will enable better matching of patients with appropriate treatments. “Then,” Dr. Espinoza says, “we could avoid much of the suffering patients experience as they go through multiple trials of medications or psychotherapy before getting to the right treatment.”

Neuromodulation Offers New Options for Treatment-Resistant Depression


Newer neuromodulation therapies, along

with refinements in older ones that deliver

electrical impulses to specific areas of the

brain, can help to restore normal function

and improve outcomes for patients with

treatment-resistent depression.

“ With neuromodulation, we can use noninvasive or minimally invasive techniques to change the levels of activity within targeted circuits of the brain that are important for treating illness, while providing clinically significant benefits, with fewer side effects.”

130250_Mag.indd 11 1/21/14 11:52 PM

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Physicians UpdateWINTER 2014

MARKETING DIRECTOR Pattie Cuen

MANAGER, MARKETING

COMMUNICATIONS Judi Goodfriend

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CONTRIBUTORS Kimberly Enard Dan Gordon

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Resnick Neuropsychiatric Hospital Earns Recognition for Quality Nursing

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Physicians Update

The Stewart and Lynda Resnick Neuropsychiatric

Hospital at UCLA has received the 2013 NDNQI

(National Database of Nursing Quality Indicators)

Award for Outstanding Nursing Quality in the

Psychiatric Hospital Category. The NDNQI Award

is presented annually by the American Nurses

Association. It recognizes programs that demonstrate

excellence in overall performance in nursing

quality indicators, based on an annual analysis

of NDNQI-participating hospitals.

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