Seven million Americans live with Alzheimer’s disease, and millions more of their loved ones carry the weight of the progressive, neurodegenerative disease. In the United States alone, the federal government spends $3.9 billion on Alzheimer’s research annually.
In books and movies, the story is usually simple: research is compiled, a discovery is made, a cure is formulated, and, instantaneously, a disease is eradicated. Reality looks a little different.
While advances continue to be made in Alzheimer’s disease research and treatment, there is no cure, and treatments don’t easily translate into the day-to-day care of Alzheimer’s patients.
For Michelle Mielke, PhD, Alzheimer’s detection, prevention and care has been at the forefront of her career. Today, Mielke conducts her Alzheimer’s research in the Innovation Quarter in Winston-Salem as chair of the Department of Epidemiology and Prevention in the Division of Public Health Sciences at Wake Forest University School of Medicine. That’s a mouthful, but public health science seeks to improve health by studying entire communities or populations and getting their findings into the hands of the medical professionals treating people.
Mielke and her department continually investigate the logistics and obstacles both patients and physicians face. By examining the data from populations of people with Alzheimer’s disease, they can streamline solutions for quicker diagnosis and individualized clinical care pathways for Alzheimer’s patients.
Mielke’s Trajectory To Research
“My interest in Alzheimer’s disease goes back to my roots in small town Minnesota and my passion for neuroscience,” Mielke says. “In rural spaces like central Minnesota, there is significantly less access to care for Alzheimer’s patients, and many are encumbered by serious barriers.”
Michelle Mielke grew up in a Minnesota town of about 2,500 people. Early on, Mielke had a fascination with the brain – its structure, health and psychology. She knew she wanted to pursue an education that would provide a deep understanding of the inner workings of the brain.
In 1994, she set off for the University of Pittsburgh, where she majored in neuroscience with the goal of becoming a neurologist. During her time there, Mielke first experienced the research side of healthcare when she got a job in a work-study program about the effects of nicotine. By her third year, she was helping to plan experiments.
“Being able to see research play out in real time was thrilling, and I quickly learned I was more interested in pursuing a full-time career in research rather than medical practice,” Mielke says.
In her senior year, Mielke needed to get an additional job, so she took a nursing assistant position at a local senior living community. It was here that she developed a passion for studying neurocognitive diseases.
“There were a whole lot of patients who had dementia, and I felt like I just didn’t have the time to talk to them, to help them out as much as I would’ve liked,” Mielke says. “This experience cemented for me that dementia was the area of research I wanted to pursue.”
With clarity on her career path, Mielke headed off to Johns Hopkins Bloomberg School of Public Health, earning her doctorate in psychiatric/neuro-epidemiology. She stayed on at Johns Hopkins University School of Medicine as a post-doctoral fellow and assistant professor for four years.
It was during this time that she started leaning into what would become a major focus of her research: blood biomarkers.
How Blood Biomarkers Intersect with Alzheimer’s Research
Blood biomarkers are proteins found in the blood that can detect brain changes and are a rapidly growing method for diagnosing Alzheimer’s and other diseases. Dementia is a general term for declining memory and cognitive abilities, while Alzheimer’s is a specific brain disease and the most common cause of dementia.
In 2018, while she was working at Mayo Clinic in Rochester, Minnesota, Mielke’s research discovered that blood biomarkers (p-taus) and other biological factors could aid in the diagnosis of Alzheimer’s disease. This foundational work continues to drive her work with Wake Forest University School of Medicine.
“A big advantage of blood-based biomarkers is their accessibility,” Mielke says. “They are less costly than other types of biomarker measures to diagnose Alzheimer’s disease, and they’re generally just more accessible, particularly in rural areas where access to some of these other tests may not be available.”
While tests for these biomarkers are an important development in Alzheimer’s research, there are gaps in research and application.
“Generally, the findings of blood biomarkers have been celebrated within the Alzheimer’s field, but implementing these tests and making them accessible is easier said than done,” Mielke says.
Seeing a positive test for p-tau markers is like getting a positive test with a mammogram. A patient can receive a positive test, but may not develop symptoms of the disease. Patients with chronic conditions, including obesity and kidney disease, are more likely to receive false positives on the test readings.
Since their discovery, blood biomarker tests were most often administered within dementia clinics. Today, these tests can be acquired at the primary care level or shipped directly to consumers. This change in access means patients often come forward with preconceived care plans.
“A big concern is patients procuring and requesting these tests on their own without knowledge of the accuracy of a specific test – some are less accurate than others – or what it might mean. A person with a family history of dementia might want to know if they will develop Alzheimer’s disease. However, a positive test does not necessarily mean a person who is currently cognitively normal will develop Alzheimer’s symptoms in their lifetime,” Mielke says.
She continues: “In addition, we have learned that people who don’t have clinical symptoms but do have a positive blood biomarker result in their medical record, whether it’s a false positive or not, can be discriminated against in terms of long-term care insurance, life insurance, disability insurance and senior housing insurance.”
Having a physician’s guidance to interpret the test results (or to determine whether a test is even appropriate) while taking a full medical history into account is necessary to develop clear care pathways.
Researchers like Mielke are also asking hard questions about the application and ethics surrounding these tests as they become more widely used. For her, there are three main concerns.
“First, how accurate are they in the general population, especially among older adults with multiple chronic conditions that can affect the levels of these biomarkers? Secondly, who should receive and who should not receive the biomarker tests? You don’t want to do a test just to do a test. And then a third part is interpreting the test and trying to understand how to best develop the patient care pathway and subsequent intervention,” Mielke says.
More research is needed to make these pathways clear.
Improving the Process of Testing and Treating Alzheimer’s Patients
Using population data, Mielke and her team are working to create a standardized system for medical professionals to guide patients through the testing and diagnosis of Alzheimer’s disease.
When a person is concerned that their memory and thinking may be changing, they need to seek a medical diagnosis. And that can be a challenge. Primary care offices are often overrun with patients, and appointments are short.
Adding an additional step of administering a cognitive test to determine whether the person has objective cognitive impairment and then assessing the underlying cause of the cognitive impairment (e.g., through blood tests and other measures), requires more time from an already overburdened workforce.
To address this problem, Mielke, her collaborators and staff created an alternative pathway for diagnosing cognitive impairment earlier and understanding the cause, involving nurse practitioners instead.
Nurse practitioners using telehealth mechanisms to reach rural areas have more time to assess the underlying causes of cognitive changes including depression, sleep problems, substances, medications that can impact cognition and uncontrolled vascular factors. They can order p-tau tests as part of standard blood draws and subsequently follow-up with additional testing as needed. Nurse practitioners report all findings back to the primary care physicians so that they can best treat and care for the patients.
This can expedite a referral to a dementia specialist for those who need it, allowing patients to receive expert care more quickly, which can provide relief for patients and their caregivers.
Researching in a Unique Environment
As a part of the Division of Public Health Science, Mielke works alongside a collaborative force of scientists, researchers, physicians and healthcare providers that studies the real-time clinical pathways patients undergo to gain access to these treatments and any barriers in their way.
“I really love working at Wake Forest University School of Medicine. Everyone here has an emphasis on collaboration, and my colleagues and I don’t experience the silos that often happen within similar institutions across the nation,” Mielke says.
While the collaborative spirit of the School of Medicine is a high point for Mielke, what first attracted her to Winston-Salem was the data.
Mielke brought her research to the iQ in 2022. When Wake Forest Baptist Health, including Wake Forest University School of Medicine, joined forces with Atrium Health (part of Advocate Health) in 2020, it gave the School’s researchers access to a larger, more varied research population and expanded database of electronic health records. This pool of knowledge was a significant draw for Mielke.
In the growing knowledge community of the iQ, Mielke continues to research how to improve the process of diagnosing and treating Alzheimer’s disease, but it isn’t the only aspect of her work.
Pushing for Public Health Progress
In addition to her research on blood biomarkers, Mielke is the director of Real-world Advocate Data for Research (RADAR) that supports Advocate Health National Center for Clinical Trials. RADAR examines electronic health record data and external data to study neurodegenerative diseases and their effects on the larger population. Mielke and her team work within Winston-Salem’s population to help with recruitment for trials, determine eligibility, and help conduct research on reactions to neurodegenerative disease drugs.
“We track what happens in studies where recipients are exposed to new drugs; both the immediate reactions and reactions over the course of months following. Not only are we noting effects and reactions, but we are also looking at insurance issues, pharma boundaries and ways to intervene in patient pathways,” Mielke says.
Her work with RADAR not only helps gather and report on this data on a national scale, but also requires collaboration across Advocate Health, Wake Forest University School of Medicine and industry partners–which comes more naturally within the culture of the iQ.
“Being able to access the data available through Advocate Health has been critical in moving the science forward to advance patient care. They have reliable and consistent EHR (electronic health records) that inform our studies,” Mielke says.
Embracing Innovative Community
When she’s not researching, Mielke actively explores Winston-Salem. She and her family spend much of their time running, biking and hiking. Early on, they were impressed by the integration of murals, sculptures, art and green spaces as part of their active lives around the iQ.
“Winston-Salem has been my favorite place to live, and I’m not just saying that. When you’re out running, people will genuinely stop to say hello or offer a wave. There’s a natural, heartwarming community here,” Mielke says.
With a view of the iQ from her office, Mielke is surrounded by progress and collaboration on all fronts. Surrounded by growth in the iQ and looking toward the future, Mielke is eager to watch her department expand, increasing faculty and staff and gaining insights across industries.
“The idea behind the iQ is fantastic, a central space where industries can collide and collaborate. Being in the iQ gives me a lot of hope and excitement for the future,” Mielke says.
