Living with Lewy Body: A Neurologist’s Journey Through Research and Dementia Care

Intro: I’m Dr. Nathaniel Chin, and you’re listening to Dementia Matters, a podcast about Alzheimer’s disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news in Alzheimer’s disease research and caregiver strategies. Thanks for joining us.

Dr. Nathaniel Chin: Welcome back to Dementia Matters. Today I’m joined by Dr. Sara Langer, a neurologist from Minnesota. At age 50, she noticed changes in her cognition, or thinking ability, and began struggling with work. Knowing her family’s history of dementia, with the condition affecting her great-grandmother, father and two sisters, Dr. Langer started on her journey to learn what was causing these changes. She met with many experts in the field, but none would diagnose her with dementia, instead stating her changes were symptoms of other health-related issues – migraines, medications, menopause and more. She also turned to research, hoping to learn more about what was happening by becoming a research participant at her local Alzheimer’s Disease Research Center, or ADRC, but was told that the center wasn’t willing to disclose results to research participants. It wasn’t until she pursued her own testing with a primary care provider and neurologist that she was eventually diagnosed with Lewy body dementia, or LBD. Having navigated the challenges of clinical care and research, Dr. Langer now hopes to help break down silos between care and research by encouraging the field to expand diagnoses to more than criteria and to share results back to research participants. Thank you for joining us today, Dr. Langer.

Dr. Sara Langer: So happy to be here

Chin: Along with me is Dr. Sarah Walter, program administrator for the Alzheimer’s Clinical Trials Consortium and the Alzheimer’s Therapeutic Research Institute (ATRI) at the University of Southern California. She joins me as well to be the co-host of this series. It’s always a pleasure to have you on, Dr. Walter

Sarah Walter: Thanks, Nate.

Chin: So I’m gonna start with you, Dr. Sara Langer. You are a neurologist, so an expert in the brain. But more than that, you are an expert because you are living with the changes that happen when the brain doesn't work as it should. If you could take this time and share with us how you came to this diagnosis of Lewy body disease as the patient.

Langer: Well Nate, as you stated, I have a family history of a non-Alzheimer's dementia affecting probably four consecutive generations on my father's side of the family. My father was undiagnosed until his postmortem exam in 2008. Around that time, I was noticing significant difficulty with complex attention and visual-spatial dysfunction at age 51, so I arranged for my first neuropsychological test. Although the testing disclosed subtle difficulties with attention and visual-spatial tasks, the neuropsychologist attributed these findings to anxiety and inadequate sleep, possibly related to menopause. I quit my job for a year to see if my symptoms improved. They didn't. When I followed up for repeat neuropsychological testing 18 months later, the same findings were then attributed to my migraine medications and continued sleep problems. I was urged to return to work very part-time, which I was thrilled to do because I loved work. However, over the next three work years, I had increasing cognitive difficulty. Despite assurances from my colleagues that they saw no decline in my work, I was convinced I was developing dementia with Lewy bodies and I resigned at age 56. By the time I was 57 or 58, it was apparent to me that two of my three sisters were increasingly impaired by the same symptoms. I consulted a local neurologist, then two behavioral neurologists with expertise in dementia with Lewy bodies at leading academic medical centers. Both downplayed my description of my symptoms and subtle but clearly abnormal findings on neuropsychological, autonomic, FDG PET, CSF, and physical examination. The second behavioral neurologist told me he would know what my diagnosis was on autopsy. Although a very attentive movement disorders specialist in California who I sought out diagnosed me with dementia with Lewy bodies when I was 61, circumstances arose that I had to see a new neurologist a year later. Subsequently, I consulted two more academic movement disorder specialists who did not feel they could make a diagnosis of dementia with Lewy bodies (DLB) and really didn't offer very much in the way of symptomatic management. So I returned two years ago to my hometown and asked a former colleague of mine to take on my care. She agreed with the diagnosis of DLB, and as an expert in sleep disorders, she really listened to my history of sleep difficulties and made the diagnosis of REM Behavior Disorder (RBD) based on my description and classic findings on polysomnography. So, it's been a long journey, and without my family history to guide me, without my own neurological background, I think it would have taken me even longer to arrive at this diagnosis.

Chin: Well Sara, thank you for sharing that story, and I imagine that was not an easy thing to put together considering you span over a decade in telling that story, but also it's very personal, and I imagine there are a lot of road bumps and barriers for you. When I hear you talk about this process it's very clear that getting the diagnosis was not easy and it took many specialists. It took a lot of your own time and energy within the context of having this training and degree in neurology. What stands out most to you in this clinical process? And in this part, feel free to put on the hat of the clinician, the neurologist, or that of the patient.

Langer: Well I think that my concerns about the process are that my very specific subjective cognitive complaints were not taken seriously as they did not conform to the very sketchy descriptions out there for classical hallucinations, classical difficulties, and that despite my demonstrated subtle but abnormal findings on various objective tests, the experts were too reliant on a very few insensitive diagnostic tests that are used to include people in their clinical research. Namely, the presence of a DaTscan to confirm dopamine deficiency, a radionuclide scan called MIBG, which becomes positive eventually in many people but is not positive early in the course of the disease, and a number of other tests that they chose not to get or whatever because they didn't recognize that my symptoms or findings were representative of the true spectrum of the disorder.

Walter: Thank you, Dr. Langer, for that. Thinking now about research, and it's clear you spent a lot of your own time searching for information and for answers, but what was it that motivated you to enroll into clinical research? Were you hoping to receive a diagnosis or some confirmation there?

Langer: The main reason I enrolled was to find out why there is such a strong familial predisposition to this disease in my family. I've encountered many other individuals with dementia with Lewy bodies in their 40s, 50s and early 60s who also have consecutive generations of affected family members. Many like mine do not develop overt dopamine deficiency until either evident by DaTscan or evident by the presence of cogwheel rigidity or the characteristic rest tremor; they can be otherwise very Parkinsonian, but without those findings they are not characterized as being Parkinsonian by the clinician researchers because, again, those are the criteria for inclusion into their protocols. So these people do not receive a diagnosis. That was another motivation. Finally, I'd like to say that I was hoping to have some of the tests that are done for non-Alzheimer's related dementias that are only available through participation in research. Although I found out that these research results would not be disclosed to me, I wanted the opportunity, if not to discuss those particular results, but to at least discuss my clinical course and my observations with experts in the field.

Walter: It's clear that you put a lot of energy into finding research in Lewy body dementia. What I've observed, of course, is that a lot of research is really focused on Alzheimer's disease. So, as somebody living with a diagnosis of Lewy body, what would you like to see to expand our focus beyond that of Alzheimer's disease and research?

Langer: The field of adult-acquired neurocognitive disorders is so huge, nuanced, wonderful, that it's hard to give a concise comprehensive answer. But I believe that as our understanding of neurodegenerative processes and our diagnostic acumen improves, the proportion of people with generic Alzheimer's disease and generic vascular dementia will probably decrease. Already the coexistence of mixed pathologies among adults over 60 is gaining a lot of traction. I think compared to the past, proportionately more adults with acquired progressive cognitive decline will be recognized as having a variety of other pathologies, including autoimmune diseases, chronic traumatic encephalopathy (CTE), and toxic exposures, among others. As sex-related brain defenses become more well-defined, we will see more women diagnosed with frontotemporal dementia and dementia with Lewy bodies because they often present differently than men, and those diseases have classically been defined according to signs and symptoms most obvious in men. For example, in autonomic dysfunction, no woman I know has ever been asked about her ability to have an orgasm, although most men are asked about erectile dysfunction. Another example is in the field of chronic traumatic encephalopathy. Women have been underrepresented in terms of numbers suffering from CTE because although they less often box, play football or are involved in military combat, they are disproportionately victims of domestic violence and equally susceptible to head injuries from things like epilepsy and car accidents. So I think that the field of neurodegenerative diseases depends on better understanding the variables of sex, genetics, epigenetics, environmental and social determinants of health and I'm looking forward to greater international collaboration and research and use of more specific tools to begin to make important distinction among these mechanisms and diseases.

Chin: That is so well said, Sara. I appreciate you saying that and it leads into my other question, which is, what do you think researchers and research centers like the Alzheimer's Disease Research Network, what can they do better right now for people who don't have the typical Alzheimer's disease symptoms?

Langer: In order to better understand non-Alzheimer's diseases better, I think researchers need to spend more time in discussion with participants to learn their histories, which includes, of course, not just a focus list of questions but their medical, family, social and occupational histories in more detail. The really good diagnosticians do not simply check off boxes on a list. They think about the sensitivities and limitations including potential biases of the tests they administer. In discussing test results with participants, not only do the participants become more educated, but the researchers learn additional useful information. Our knowledge base grows as researchers discover trends not anticipated or quantitatively captured in their study designs.

Walter: Sara, if someone came to you with some thinking problems and a desire to learn more about research, what would you advise them about the process?

Langer: My advice would be to look for programs that have effective people communicating the study process – its purpose, the timeline, its requirements, including time commitment, tests, risks, the opportunity to meet with clinicians, and discussion of results. Before deciding to commit I'd make sure that I have my questions answered. Although not all research protocols will be able to share individual results, I want to make sure that the study coordinators were invested in educating the participants about some conclusions of their work even before publication. Those are just some of the things that I would look for in participating in research. Despite my difficulties at different times with the process, I still believe that our understanding of the true nature of neurological disease is going to come about as a result of this sharing of insights among researchers and participants.

Walter: Research is trending towards a more narrowed focus on dementia, studying it in its purest form. What do you think about the impact this is having on the field and what we're able to learn from those studies?

Langer: I am fully aware of this forced dichotomy between having a limited number of variables in your study design, but I worry that certain intrinsic biases, certain assumptions made that are part of the study design, actually may lead one away from truly meaningful results. Let me give you an example. In many, many studies of dementia with Lewy bodies, they use the Mini-Mental State Exam (MMSE) or MoCA exam as their test of cognitive function. Well, in fact, if you really want to look at dementia with Lewy bodies, you would be looking pretty much exclusively at complex attention, visual spatial function and, later on, executive dysfunction. Executive dysfunction is not a very early finding in Lewy bodies, but it is present by the time dementia is apparent. So there's assumptions or bias there that you know – of course, they're not going to show in a period of testing a medication for nine or twelve months that there's been a change in their Mini-Mental State Exam or MoCA because the data is lost using that tool. So that's one very crude example. I think the same can be said of inclusion and exclusion criteria that they make on individuals based on certain perceived test findings that may be insensitive or interpretations of their symptoms which are, again, influenced by sex and socioeconomic factors.

Chin: Sara, I'd like to know how you felt being on the receiving end when a physician or clinician tells you about other suspected causes. In your course, in this process of eventually learning you had Lewy body disease, you were told, “Well it could be stress so you should retire,” or, “Not enough stimulation so come back to work,” or medications, the migraines, just the menopause in general. I'm sure as a clinician you have said some similar things to patients looking at different possibilities, but what was it like to be on that receiving end as you were going through this whole thing?

Langer: At its most basic level, it was very frustrating. On the other hand, I recognized that I am among the luckiest people who have this condition because there was a certainty. Despite whatever anybody else said, I knew that there was validity in my family history having watched my grandmother and father go through this process and intimately knowing that my father's autopsy validated what was really classic neuropsychological findings. My father, who was a radiologist with an appointment in medical genetics, ordered his own PET scan, FDG PET, which was read out erroneously as consistent with Alzheimer's disease. But that was back in the early 2000s and the cingulate island sign wasn't described until 2008 or 2009. He knew he did not have Alzheimer's disease and that's what he was told. He knew that there was some strange genetic predisposition in our family. He left a paper trail for me, and that's exactly what I am doing for my children, their cousins and a multitude of other families in the same position.

Chin: Sara, I have a question about the difficulty in coming to a diagnosis when a person presents so early in the change. You are a perfect example of someone who clearly has the training, the expertise, the self-reflection, but also the family history that would make one more vigilant. But when you presented, as you said, your symptoms were mild, your cognitive testing results were mild, even the biomarkers – these fancy scans and lumbar puncture, spinal fluid analysis that was done – everything was sort of mild. In this field where people want definitive answers, how do you reconcile that the field just isn't there to be able to sort through all of these things, that there is uncertainty. How do we express that, or should we express that? How did you go through that? Knowing what you know now, what would be different for you?

Langer: This is real life, it is not black and white. Therefore the clinician and patient acknowledge that, “You know what, this isn't textbook, but there are real concerns here.” Even though you may not fulfill research criteria in order to be enrolled in a clinical research trial, which I'm fine with, there are many things that we can do to make your life optimal and whatever is optimal for you. So personalized medicine is critical here. It may not be the same prescription that you write for everybody with dementia with Lewy bodies or Alzheimer's disease or whatever it is, but it is addressing the nuances that are significant in that individual's life to allow them to live most prosperously.

Walter: That’s beautiful, Sara.

Chin: Well I want to thank you, Dr. Sara Langer, for being on this podcast. You've said so many thoughtful things here and I know that our listeners are going to appreciate that. I know all of our participants will appreciate hearing your insights and for you also sharing your story, so thank you for doing that and we certainly value your perspective and experience.

Langer: Thank you so much for this opportunity.

Walter: Thank you.

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