Unlocking the Secrets of the Brain
Faculty researchers are uncovering clues to the mystery of how the brain affects health throughout the body.
Is heart failure a disease of the brain? Before you answer “Of course not, it’s a disease of the heart,” you need to talk to UCLA School of Nursing Professor Dr. Mary Woo, whose research focuses on the correlation between brain abnormalities and cardiovascular disease.
“Heart failure patients characteristically have disturbances in sleep and breathing patterns, and they have a very high incidence of depression,” she explains. “They also have many difficulties with cognition and motor coordination, such as memory loss and balance problems.” When Woo first began to study this perplexing set of concurrent symptoms, she quickly arrived at one inescapable conclusion: “Something’s wrong with the brain in heart failure.”
Woo is one of several faculty members at the school who are conducting pioneering interdisciplinary research that examines the complex role the brain plays in health, illness and wellness across the life span. From deciphering that mysterious link between brain dysfunction and heart malfunction to understanding the early molecular changes that precede the development of Alzheimer’s disease, these SON scientists are collaborating with biochemists, neurobiologists, psychologists, and other experts to lead translational research studies with enormous potential to transform current treatment strategies and dramatically improve health outcomes.
Hearts and Minds
“Heart failure is the number one hospital discharge diagnosis for people older than age 65,” says Woo. “It costs Medicare alone more than $33 billion a year. Yet despite all the advances in treatment
that have emerged in the last 10 to 15 years, the high rates of mortality and morbidity in heart failure haven’t changed. And that situation isn’t going to improve until clinical practice starts to address the compounding factors that are contributing to that morbidity and mortality—namely, the considerable amount of brain damage we’re seeing in these patients.”
Groundbreaking initial studies by Woo and her team have revealed that heart failure patients have injuries and functional abnormalities in regions of the brain that control mood, memory, decision making, blood pressure, heart rate and breathing. Now she’s digging deeper to find answers to questions like: What exactly is causing this damage? Which comes first, the brain dam- age or the heart failure? And how do all the different clinical pieces of the puzzle—depression, sleep-disordered breathing (SDB), memory impairment, etc.—fit together?
“Before we can treat these problems in the brain, we need to know what’s causing them,” Woo says. Her ultimate goal is to translate the answers into new heart failure treatments that can improve survival rates and quality of life for this extremely vulnerable group of patients.
Woo is currently working on several studies, funded by the National Institute of Nursing Research (NINR), that are already testing possible therapeutic interventions on a variety of fronts. For example, she is working on whether improving respiration in heart failure patients with SDB could reduce some of their risk for poor outcomes.
She has also found evidence that vitamin B1 (thiamine) deficiency is connected to memory loss in people with heart failure. “They can’t absorb nutrients properly, because of the diuretics they take,” Woo notes. “Thiamine deficiency is also associated with memory loss in alcoholics. With our heart failure patients, we’ve found that thiamine levels and the amount of brain damage are directly linked. So the next thing to look at in terms of interventions is treating them with thiamine supplements.”
One of the most practical clinical implications of Woo’s work is that standard patient education methods simply won’t work with this population. “When you’ve got patients who have substantial brain damage that affects their decision making and memory, it’s not likely to be effective to talk to them about self-care instructions and expect them to remember anything,” she emphasizes. “There needs to be an immediate change in practice if we’re going to stop these patients from bouncing in and out of the hospital like ping-pong balls and help them live independent lives.”
Teens in Transition
Dr. Nancy Pike, Assistant Professor at the school, is also studying the impact of cognitive impairment on cardiac patients’ self-care skills. But Pike’s biobehavioral research centers on a younger—though equally high-risk—patient profile: adolescents who were born with congenital heart disease (CHD).
“A generation ago, most of these children died shortly after birth,” she says. “But now that they’re surviving, they face the challenge of having to take responsibility for their own health as they transition out of their parents’ care and into adulthood.” Unfortunately, too often these young chronic heart disease patients become lost to follow-up— they stop going to the doctor and neglect their symptom management regimens. And when that happens, their mortality rates skyrocket.
“We know that cognitive deficits, particularly memory loss, are common in adolescents with CHD and can significantly affect their ability to care for themselves,” Pike says. “However, it’s uncertain if their memory deficits are associated with brain structure or with brain injury resulting from their having had multiple heart surgeries at a young age.”
She is now in the second year of an NINR-funded study that’s the first of its kind to examine the relationship between a clinical symptom—in this case, memory loss—and brain structure in teenagers with CHD. Pike and her colleagues are using MRI techniques to compare parts of the brain that control memory, such as the hippocampus and the mammillary bodies, in groups of adolescents with and without CHD.
“Instead of just brushing this behavior off as ‘the forgetful teen,’ there may be a valid reason why this is happening,” she concludes. “If we can make that correlation between brain injury and the memory problems, we can look at interventions that could improve memory and self-care ability in this growing population of CHD survivors.”
Treating Alzheimer’s Before It Starts
Loss of synaptic function in nerve cells in the brain is one of the first signs of Alzheimer’s disease pathology, occurring long before the formation of the amyloid-beta (A-beta) plaques that advance the progression of this devastating form of dementia. Two faculty members at the school, Professor Dr. Karen Gylys and Assistant Professor Dr. Sophie Sokolow, are trying to find out what’s behind these preliminary brain changes that cause synapses to degenerate. The results of their research could help open the door to the development of revolutionary new drugs for treating Alzheimer’s in its earliest stages, when plaque buildup and cognitive loss can still be reversed—or even prevented.
“If we scientists can understand what’s going wrong with the synapses, we could find a way to protect them,” says Gylys. “Any drug therapy that’s going to be effective needs to work early and target the synapses. Once you get to the point where a lot of synaptic pathology has occurred, it may be too late.”
Although both researchers are exploring the same issue, they’re approaching it from different perspectives. Sokolow, a pharmacologist, is looking at whether factors like disrupted calcium regulation in neurons and A-beta buildup in synapses are possible molecular triggers for Alzheimer’s. Gylys, a nurse who has a background in neuroscience and pharmacology, has just completed a study, funded by the National Institute on Aging, that sheds light on how cholesterol and ApoE (a lipoprotein that carries cholesterol through the bloodstream) contribute to A-beta accumulation in synaptic terminals.
The next phase of Gylys’ research is to learn more about how the cholesterol connection could eventually lead to ApoE-related therapies for keeping the brain healthy, such as treating early-stage Alzheimer’s disease patients with cholesterol-lowering drugs.
“There’s a lot of promise and potential for drugs that affect ApoE and its pathways,” she says. “We know that some forms of the ApoE gene, particularly ApoE-e4, increase the risk for Alzheimer’s, whereas the ApoE-e2 form is protective. So that’s something we want to follow up on.”