Safely Disclosing Amyloid Results with Alzheimer’s Disease Research Participants

dr lindsay clark
Lindsay Clark, PhD

Dr. Lindsay Clark’s new study will evaluate the psychological consequences of disclosing amyloid test results to cognitively unimpaired adults. Dr. Clark joins the podcast to define amyloid accumulation and discuss how her study will examine the process of revealing amyloid results to research participants in Alzheimer’s disease research studies. Guest: Lindsay Clark, PhD, assistant professor, University of Wisconsin School of Medicine and Public Health

Episode Topics:

  • What is amyloid accumulation and its relationship to Alzheimer’s disease? 1:13
  • How are you measuring amyloid in living people? 3:14
  • Are newer methods like PET scans reliable? 5:56
  • Do patients learn the results of these scans? 6:20
  • Do research participants ever learn their results? 7:30
  • Who is the target population for studying amyloid scans? 8:44
  • Why does disclosing the results take so many careful considerations? 9:35
  • What do you think are the components of a good disclosure? 11:48
  • Are you disclosing specific numbers of the results? 14:16
  • Why does your study focus on amyloid PET scan results? 16:31
  • Do you believe the key concepts of disclosure can work with other biomarker studies? 18:33

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Show Notes

Learn more about Dr. Clark's Amyloid Disclosure Study.

Listen to another Dementia Matters episode on the topic of disclosing Alzheimer's disease risk to research participants, "The Power of Disclosure: How Explaining Risk of Alzheimer's Disease Impacts Life Afterward."


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: My guest today is Lindsey Clark, a geriatric neuropsychologist and Alzheimer's disease researcher at the University of Wisconsin. Dr. Clark assesses, treats, and counsels patients with memory concerns, cognitive changes, and other neurological conditions at the UW Geriatric Memory Assessment and Follow-Up Clinics as well as the William S. Middleton Memorial Veterans’ Hospital in Madison. One of Dr. Clark's research interests is developing strategies for safe disclosure of Alzheimer's disease biomarker information. Today we are going to discuss a new amyloid disclosure study she recently launched with a select number of participants in the Wisconsin Registry for Alzheimer's Prevention, or WRAP Study. Welcome back to the podcast, Lindsay. 

Dr. Lindsey Clark: Hi. Thanks for having me today.

Chin: So I want you to start out by explaining amyloid accumulation and what the science community knows about its relationship to Alzheimer's disease?

Clark: Amyloid is a protein that is a part of beta amyloid plaques, which is one of the two pathologies involved in Alzheimer's disease. People with Alzheimer's disease in their brain, they develop beta amyloid plaques and neurofibrillary tangles. Beta amyloid plaques are something that develops in the brain that basically interferes with the ability of the brain cells to communicate with one another. And so what we know as a field is that these plaques start developing very early in the disease. They're probably one of the earliest brain changes that happen in Alzheimer's disease. We know that these start developing about ten to twenty years before a person develops symptoms that are significant enough to be diagnosed with Alzheimer's disease or dementia.

Chin: Okay, so just to clarify then, so Alzheimer's disease is broken down into having two abnormal proteins. One, you said, was amyloid or beta amyloid. Then the other is neurofibrillary tangles or a tau protein. Is that right? 

Clark: That's correct.

Chin: And so then the amyloid itself is one of the first things that occur in this process of building up to Alzheimer's disease, but amyloid actually forms what you said was plaque. There's little amyloid proteins that come together and form a bigger plaque, is that right?

Clark: That's right, yeah. This beta amyloid protein, for some reason it sort of goes bad in the brains of Alzheimer's disease patients. You know, they kind of get sticky and clump together and turn into these larger plaques that interfere with brain function.

Chin: And these plaques then can interfere with the processing and regular function of the brain?

Clark: That’s right.

Chin: Okay, and so then this amyloid is what people like you, researchers in science, are identifying and measuring in living people?

Clark: That’s right.

Chin: How are you doing that?

Clark: Yeah, so there's a couple of different techniques that we use to measure amyloid in vivo, or in living people's brains. One is using a special type of imaging – brain imaging technique called Positron Emission Tomography, or PET scans. In this method, we inject a tracer into the bloodstream of patients or participants and this tracer is specially designed to bind with beta amyloid protein in the brain so then we can see exactly where and how much beta amyloid protein is in a person's brain. It helps us to better quantify, you know, if a person has beta amyloid plaques in their brain and if so, you know, where and how much. Then the other technique that's used to measure amyloid is by doing a lumbar puncture and extracting cerebrospinal fluid out of the spinal cord. Cerebrospinal fluid is basically the fluid that surrounds the brain and helps kind of keep the brain protected within the skull. By extract – doing a lumbar puncture to extract that fluid, we can see a little bit more about what proteins are actually happening or, you know, actually present in the brain. That's another technique that's used to see if there's abnormally low levels of amyloid protein. In the cerebrospinal fluid which would suggest that it's actually being kind of stuck within the brain. Normally the brain kind of flushes out this amyloid protein, but if the protein's getting stuck in these plaques then it doesn't flush it out as efficiently. And so we see lower levels of this protein in the cerebrospinal fluid. We can also look for other proteins like the tau protein that's involved in neurofibrillary tangles using that technique as well.

Chin: And so prior to being able to do spinal fluid analysis and the PET scans, we relied on autopsies, pathologists looking at people who just died and looking for these proteins. Is that right?

Clark: Yeah, it's only recently, you know, in the last decade or so that we've been able to see some of these protein changes in living people. It used to be that we had to wait until people passed away and then look in the tissue after death to determine whether amyloid or tau is present.

Chin: Okay, well. So are these newer techniques, like the PET scan and the spinal fluid, are these reliable?

Clark: They are. Yeah, they've been studied across many labs and the techniques have been refined and kind of validated in many different ways and so they are reliable measures of amyloid and tau proteins in the brain.

Chin: And so knowing that then, in your time in clinic do patients ever learn about the results of these types of scans?

Clark: You know, that's a good question. These aren't typically techniques that we are using in the clinical setting. Usually in the clinic people might have other tests, like MRI scans to look at just overall brain structure, but these aren't typically used as much in a clinical setting. Part of that is related to insurance doesn't cover most of these techniques, for example amyloid PET scans. Some clinics will order CSF results, but this is not very common. I think there's kind of similar issues in terms of insurance coverage so it's just not something that's used as much in a clinical setting at this point. Now, there are studies being conducted by Medicare and Medicaid services to determine the clinical utility of amyloid PET scans and whether they would want to potentially cover them in the future, so it's possible this might change.

Chin: And then jumping from the clinic into the research world, do research participants learn about the results of their amyloid PET scan or their CSF findings?

Clark: Typically if it's being done in an observational study, the research participants are not informed of these results. In clinical trial settings, there are times where it's a part of the study to inform participants of their results. For example, in studies in which participants have to be elevated – have to have elevated amyloid in the brain in order to participate in the clinical trial because it's an anti-amyloid therapy. In those studies participants are informed of the results because if they're not elevated then they're usually not enrolled in the clinical trial, and so they have to be told those results. In observational studies in the past, participants have typically not been informed of any research results unless they're clinically relevant. So, you know, if a brain tumor is found on an MRI Scan or something that can be intervened on is found on their labs, for example.

Chin: In Alzheimer's disease research, who is the target population for using amyloid scans and studying them?

Clark: Often the target population is individuals who are at higher risk for Alzheimer's disease. People who are maybe in their fifties or sixties who have a family history of Alzheimer's disease, for example. Many of the studies using these biomarkers are looking to see if we can identify markers of the disease in the preclinical stage, so prior to symptom onset. Typically these scans are being done in that population, although there are also studies using them in individuals who have diagnoses of dementia or mild cognitive impairment as well.

Chin: And in your study, you're disclosing to participants the results of their amyloid scans. What population are you doing? And then, why does this require such careful consideration and an entire study about the strategy of disclosing this information?

Clark: For our study, we'll be disclosing amyloid PET scan results to cognitively healthy older adults who are enrolled in our longitudinal research study, specifically the Wisconsin Registry for Alzheimer's Prevention. The reason that it requires careful consideration is because we want to make sure that we're balancing the risks and benefits of disclosing these results. What I mean by that is we want to make sure that when we share this information we're doing it in a way that is not just anxiety-provoking, distressing, very worrying for people, but is also providing some sort of benefit to them in learning this information. One of the things we want to do to make sure that we are being, you know, careful is by providing a lot of education about what these results mean. The first part of the study is really doing good informed consent and providing an education session about, you know, what is beta amyloid, what are we measuring with these PET scans, and what do these results look like, because one thing that is tricky is that we don't know, on an individual level, exactly what these results will mean for people. For example, we know that if someone has elevated levels of amyloid plaque markers in their brain – so elevated amyloid PET scan results – they are at higher risk for dementia due to Alzheimer's disease, but we don't know for sure, you know, exactly – will they definitely develop dementia and when they'll develop it. So there are some challenges in terms of sharing that information with people and making sure that that's understood and clear.

Chin: What do you hypothesize are really the critical components to a good disclosure, knowing that the results from your study will impact other studies as well as potentially clinical care in the future?

Clark: Yeah I think there are a couple of really critical components to doing good disclosures. One I just briefly talked about, which is education and informed consent. Making sure that people understand what these results mean. They mean that they're at higher risk for Alzheimer's disease if the result is elevated, but doesn't mean that they're definitely going to develop dementia in the future. We want to make sure people understand that kind of gray area about these results and are still wanting this information. Doing good informed consent and education around that is really important. Then having someone who is educated or, you know, knowledgeable in this area doing the disclosure. We want someone who is kind of an expert in Alzheimer's disease and a good clinician being able to disclose the results so that when people do have questions, those questions are able to be answered and they can have a discussion about it. Also another critical component is monitoring for increases in depression or anxiety, which can sometimes happen for kind of a short period of time following the disclosure of this result. We want to make sure that we monitor that and provide support as needed. Then another potential critical component is helping people to, like, understand what other risk factors they might have for dementia, if they want to know those. That might be more modifiable factors, such as hypertension, physical inactivity, depression, stress, sleep; those kinds of other factors, maybe providing some insight on what people can do to reduce other risk factors for dementia. Kind of overall I think education and monitoring for psychological symptoms, and providing adequate support and knowledge I think is critical.

Chin: Yeah, in essence you're providing care at the end of it. You're letting people know their information and then providing care information for them afterward. What I didn't hear from you is disclosure of actual numbers or risk calculations. Are you disclosing that, and if not why not?

Clark: For our study, we're just disclosing a result that indicates whether a person is elevated or not elevated on their amyloid PET scan. The reason for that is we feel that we understand what those results mean. We can clearly determine if someone is elevated in their – on their amyloid PET scan and we do know that that's associated with an increased risk for cognitive decline and dementia. It gets a little harder when we try to quantify exact numbers. We are working on studies to do that to better delineate exactly, you know, how much for example amyloid plaque we see in the brain or the distribution of that plaque and what that might mean for a person's future. We are doing those studies in the lab but we don't have a good enough sense of exactly what those results mean in order to share that or disclose that with participants because we're still kind of forming those calculations and developing those numbers. That might be something, you know – that and then a risk calculator, in terms of kind of bringing together all of a person's risk factors, those are things that we're hoping to develop in the lab and could potentially be something that's disclosed in the future.

Chin: I think that's important for us to know in the clinics, as well as in the community, that it takes a lot of time and studies in order to come to those numbers and those risk calculations and you can't just do it haphazardly otherwise. Potentially there's harm that people could experience with that. I appreciate that you're doing it in a very methodical and careful way, even if it is slow. We know that you're working on it and so I'm glad you're able to share that. I wanted to end our interview today with just a thought and a question. There are other biomarkers for Alzheimer's disease that researchers are exploring. These are things like you mentioned tau or just neurodegeneration, brain cell death, or something that's been quite popular in the news lately, blood-based biomarkers for Alzheimer's disease. Why does your study focus on amyloid disclosure instead of one of these other biomarkers?

Clark: That's a good question. Our study focuses on disclosure of amyloid PET scan results because this technique has been around the longest. We have had amyloid PET scans since the mid-2000s. These, I think, are the most reliable, the most potential – have the most potential clinical utility. We have, kind of, the most understanding of what these results mean for people's risk for Alzheimer's, dementia. That's why we are focusing on amyloid PET scan results. The work that we do in developing procedures for disclosing amyloid PET scan results I think can be translated to other biomarkers because it's very similar. You're disclosing information about someone's, you know, changes in someone's brain and how they inform a person's risk for Alzheimer's disease. That I think – those kinds of practical guidelines that we develop and procedures we develop we can, I think, easily translate to blood-based biomarker disclosure or tau PET scan disclosure, if that were to happen in the future. Amyloid PET scans are just kind of – I feel like we have the best understanding of what those results mean and have the most competence in them, so those are where we're starting at this point. Certainly there's a lot of other biomarkers that are being developed and will have hopefully a better understanding of those in the future as well.

Chin: Do you believe you'll be able to translate the key concepts from your study with disclosure in general to these other studies?

Clark: I do, yeah. I think our understanding of how to provide good education, to do good informed consent with people, our understanding on how sharing this information impacts people's personal lives. Do people feel more motivated to engage in brain healthy behaviors, for example? Do people go out and do more long-term care planning activities? Or do people feel like they have more memory problems? You know, do they notice memory symptoms more or do they feel more anxious about it or more – have more stigma, like feel like they can't share this information with people? Those kinds of more psychosocial outcomes of disclosure that we're really interested in understanding, I do think those will have implications for other biomarker disclosures as well.

Chin: Well, thank you Lindsay for your time today and I know we will have you back when you have results to discuss and share with us. Thanks again for your time.

Clark: Thank you.

Outro: Please subscribe to Dementia Matters on Apple Podcasts, Spotify, Podbean, or wherever you get your podcasts. And rate us on your favorite podcast app — it helps other people find our show, and let's us know how we are doing. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's Disease Centers. This episode was produced by Rebecca Wasieleski and edited by Bashir Aden. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. Check out our website at You can also follow us on Twitter and Facebook. If you have any questions or comments email us at Thanks for listening.