Many say they want answers, but fewer choose to know the truth

As researchers make progress in understanding how Alzheimer’s disease develops, there are growing opportunities for healthy research participants to learn their risk of developing Alzheimer’s disease dementia in the future. While many organizations often advocate for investigators to share risk estimates with individual participants, there are ethical concerns around doing so, given that there are no medical interventions to change that risk.

A new study from Washington University School of Medicine in St. Louis examines the choices such healthy research volunteers make when given the opportunity to learn about their risk of developing Alzheimer’s disease dementia. The study is published in JAMA Network Open.

The researchers found a large discrepancy between the percentage of participants who said they would like to learn about their risk if such estimates became available and the percentage who followed through to learn those results when given the actual opportunity.

The knowledge could help researchers design studies that offer the option of receiving results in ways that don’t pressure participants into making one choice over another. The study also emphasizes the importance of ensuring participants truly want their research results because hypothetical interest does not necessarily translate into wanting to learn one’s risk of Alzheimer’s disease dementia when it is actually offered.

“In general, there is movement toward giving research participants and patients their test results, even in situations when nothing can be done with those results,” said senior author Jessica Mozersky, Ph.D., an assistant professor of medicine at the Bioethics Research Center and an investigator at the Charles F. and Joanne Knight Alzheimer Disease Research Center, both at WashU Medicine.

“But our study suggests that in sensitive cases—such as when estimating the risk of developing a debilitating and deadly disease—people should have the option to not know.”

In recent years, the National Academies of Sciences, Engineering and Medicine have recommended that research study designs in general include the option to return test results to participants, even when such results can’t be acted on. Similarly, a committee of study participants, their care partners and members of dementia advocacy organizations recently proposed a bill of rights for Alzheimer’s disease research participants that advocates for access to such results.

At the same time, ethical concerns remain because of the possibility of causing anxiety and other harm to participants who learn they are at high risk of developing a debilitating and incurable dementia. Unlike preventive options for individuals who learn they are at high genetic risk of certain cancers, for example, there are currently no approved preventive treatments or medical interventions available to stave off Alzheimer’s disease dementia.

To get a clearer picture of who declines Alzheimer’s disease dementia risk results and why, Mozersky and her colleagues turned to long-running research at WashU Medicine’s Knight Alzheimer Disease Research Center. Since 1979, the Memory & Aging Project has provided a framework to study brain function in participants as they age. Over the decades, the project has evolved and expanded into several long-running studies of the development and progression of Alzheimer’s disease, including the development of biomarker tests to determine risk.

For the current study, Mozersky’s team focused on cognitively normal volunteers who underwent a battery of tests, including genetic tests, blood draws and brain scans, from which researchers could estimate their probability of developing Alzheimer’s disease dementia over the following five years.

Participants originally joined the long-term study understanding that they would not have the option to receive their own risk results. Even so, Mozersky said, over the years many have expressed a theoretical interest in learning their results.

The study, co-led with Sarah M. Hartz, MD, Ph.D., a professor of psychiatry at WashU Medicine, offered results to a subset of participants in the Memory & Aging project—274 participants—to assess the psychological impact of learning their risk, and the factors they consider when making that decision.

Before deciding, participants received an information guide explaining how risk is estimated and listing some examples of pros and cons of learning their results. For example, on the pro side, some people may learn their risk is lower than they might have expected. And if biomarker test results suggest a participant is at high risk of developing Alzheimer’s disease dementia over the next five years, they may become eligible to participate in clinical trials of investigational prevention strategies.

On the other hand, knowledge of high risk may cause anxiety or complicate the purchase of some types of insurance.

When the results were theoretical, 81% of people in the larger, long-term research said they would choose to know. In contrast, when real results were offered to the 274 participants in the Memory & Aging Project, only 60% opted to receive them. Participants with a parental history of Alzheimer’s disease and participants who self-identified as African American were more likely than others to decline the results.

A sample of participants who declined to learn their results were interviewed afterward, and the most common reasons given included that knowing would be a burden to themselves or their family members, their own negative experiences and perceptions of Alzheimer’s disease dementia, that they feel good about their memory currently, that they’re already prepared for the disease, and that there is still uncertainty in predictions of disease risk.

“The lack of preventive treatments is also a big factor in declining to receive the results of biomarker tests among people without symptoms of Alzheimer’s disease dementia,” Mozersky said.

“When we conducted interviews with some participants to better understand their choice not to know, many said that a new effective treatment might change their mind, if it became available.”

Because the results are only available through research studies, they are not added to the participant’s medical record by the investigators. Still, such results could end up in a patient’s medical record if a participant shares them with their doctor.

“We plan to continue our research into the complexities of these questions, especially as returning results to research participants becomes more common, even if those results can’t be acted on yet,” Mozersky said.

As researchers make progress in understanding how Alzheimer’s disease develops, there are growing opportunities for healthy research participants to learn their risk of developing Alzheimer’s disease dementia in the future. While many organizations often advocate for investigators to share risk estimates with individual participants, there are ethical concerns around doing so, given that there are no medical interventions to change that risk.

A new study from Washington University School of Medicine in St. Louis examines the choices such healthy research volunteers make when given the opportunity to learn about their risk of developing Alzheimer’s disease dementia. The study is published in JAMA Network Open.

The researchers found a large discrepancy between the percentage of participants who said they would like to learn about their risk if such estimates became available and the percentage who followed through to learn those results when given the actual opportunity.

The knowledge could help researchers design studies that offer the option of receiving results in ways that don’t pressure participants into making one choice over another. The study also emphasizes the importance of ensuring participants truly want their research results because hypothetical interest does not necessarily translate into wanting to learn one’s risk of Alzheimer’s disease dementia when it is actually offered.

“In general, there is movement toward giving research participants and patients their test results, even in situations when nothing can be done with those results,” said senior author Jessica Mozersky, Ph.D., an assistant professor of medicine at the Bioethics Research Center and an investigator at the Charles F. and Joanne Knight Alzheimer Disease Research Center, both at WashU Medicine.

“But our study suggests that in sensitive cases—such as when estimating the risk of developing a debilitating and deadly disease—people should have the option to not know.”

In recent years, the National Academies of Sciences, Engineering and Medicine have recommended that research study designs in general include the option to return test results to participants, even when such results can’t be acted on. Similarly, a committee of study participants, their care partners and members of dementia advocacy organizations recently proposed a bill of rights for Alzheimer’s disease research participants that advocates for access to such results.

At the same time, ethical concerns remain because of the possibility of causing anxiety and other harm to participants who learn they are at high risk of developing a debilitating and incurable dementia. Unlike preventive options for individuals who learn they are at high genetic risk of certain cancers, for example, there are currently no approved preventive treatments or medical interventions available to stave off Alzheimer’s disease dementia.

To get a clearer picture of who declines Alzheimer’s disease dementia risk results and why, Mozersky and her colleagues turned to long-running research at WashU Medicine’s Knight Alzheimer Disease Research Center. Since 1979, the Memory & Aging Project has provided a framework to study brain function in participants as they age. Over the decades, the project has evolved and expanded into several long-running studies of the development and progression of Alzheimer’s disease, including the development of biomarker tests to determine risk.

For the current study, Mozersky’s team focused on cognitively normal volunteers who underwent a battery of tests, including genetic tests, blood draws and brain scans, from which researchers could estimate their probability of developing Alzheimer’s disease dementia over the following five years.

Participants originally joined the long-term study understanding that they would not have the option to receive their own risk results. Even so, Mozersky said, over the years many have expressed a theoretical interest in learning their results.

The study, co-led with Sarah M. Hartz, MD, Ph.D., a professor of psychiatry at WashU Medicine, offered results to a subset of participants in the Memory & Aging project—274 participants—to assess the psychological impact of learning their risk, and the factors they consider when making that decision.

Before deciding, participants received an information guide explaining how risk is estimated and listing some examples of pros and cons of learning their results. For example, on the pro side, some people may learn their risk is lower than they might have expected. And if biomarker test results suggest a participant is at high risk of developing Alzheimer’s disease dementia over the next five years, they may become eligible to participate in clinical trials of investigational prevention strategies.

On the other hand, knowledge of high risk may cause anxiety or complicate the purchase of some types of insurance.

When the results were theoretical, 81% of people in the larger, long-term research said they would choose to know. In contrast, when real results were offered to the 274 participants in the Memory & Aging Project, only 60% opted to receive them. Participants with a parental history of Alzheimer’s disease and participants who self-identified as African American were more likely than others to decline the results.

A sample of participants who declined to learn their results were interviewed afterward, and the most common reasons given included that knowing would be a burden to themselves or their family members, their own negative experiences and perceptions of Alzheimer’s disease dementia, that they feel good about their memory currently, that they’re already prepared for the disease, and that there is still uncertainty in predictions of disease risk.

“The lack of preventive treatments is also a big factor in declining to receive the results of biomarker tests among people without symptoms of Alzheimer’s disease dementia,” Mozersky said.

“When we conducted interviews with some participants to better understand their choice not to know, many said that a new effective treatment might change their mind, if it became available.”

Because the results are only available through research studies, they are not added to the participant’s medical record by the investigators. Still, such results could end up in a patient’s medical record if a participant shares them with their doctor.

“We plan to continue our research into the complexities of these questions, especially as returning results to research participants becomes more common, even if those results can’t be acted on yet,” Mozersky said.