The Youngtimers Guide to Genetic Testing

Part 1

This guide is for individuals who are at-risk of inheriting a mutation that causes autosomal dominant young onset dementia, such as early onset familial Alzheimer’s disease (EOFAD). How do you know if you might be at-risk for EOFAD? If you observe at least two generations of family members with symptoms suggestive of Alzheimer’s disease before the age of 65, then it could indicate that you and your relatives are at-risk.

If you are unsure whether you or your family are at-risk, a genetic counselor can help you determine this and if predictive genetic testing is appropriate for you. To contact and speak with a genetic counselor about your own circumstances, go to our Find a Genetic Counselor page.

Individuals with a family history of EOFAD have a 50% chance of inheriting a mutation in one of three genes: amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). This guide was written to help those individuals decide whether they are ready to find out if they carry the mutation, whether genetic testing is right for them and what they can expect from testing. However, this guide does not replace professional genetic counseling.

Introduction

Since discovering the mutations that cause EOFAD, scientists and clinicians are now able to perform genetic testing – a procedure used to determine whether a person carries an EOFAD mutation in their DNA. In the image below, you can visualize where mutations are found in EOFAD individuals; they are located in one of three genes: APP, PSEN1, or PSEN2.

For more information about the difference between mutations and genes, go here .

Image 1: Visualizing where the APP, PSEN1, and PSEN2 genes are located in a person’s chromosomes

If genetic testing is done on a person who is at-risk of developing EOFAD but who is not currently showing signs or symptoms of disease, it is called a predictive genetic test or a pre-symptomatic genetic test. The result of this test predicts whether a person will or will not be affected EOFAD. People who have a predictive genetic test for EOFAD most likely have a close family member who has been diagnosed with the disease.

It is important to point out that a predictive genetic test is different than a diagnostic genetic test or symptomatic genetic test. A diagnostic genetic test involves testing a person who is already showing signs and symptoms of EOFAD. This test is usually performed in order to assist with disease diagnosis. If the result is positive (or the person has a mutation in their DNA), the result of this test confirms a diagnosis of EOFAD. This process involves several assessments with a doctor and is very different from the process of predictive genetic testing.

What is predictive genetic testing?

You may hear people say they “have the gene” or say they want to find out if they “have the gene” for EOFAD. However, what people mean when they say they “have the gene” is that they have a genetic mutation in one of the three genes (APP, PSEN1, and PSEN2) associated with EOFAD. A genetic mutation in one of these genes means the gene does not work properly. Predictive genetic testing can tell someone if they carry a genetic mutation in one of these three genes.

Does predictive testing tell me if I “have the gene”? 

One of the primary reasons people with a family history of EOFAD decide to undergo genetic testing is that this information can be critical to making important and informed major life decisions. For example, finding out your genetic status could be helpful in making family planning decisions, deciding whether to join a clinical trial, or deciding what career to pursue. For individuals who like to plan ahead, this information can aid in making financial planning decisions, including caregiving arrangements. From our conversations with other Youngtimers who pursued genetic testing and responded well after finding out their result (including finding out that they carry a mutation that causes EOFAD), many of these individuals state that knowing their genetic status gave them essential knowledge to make a more informed decision about their future.

 

On the other hand, studies have shown that some people who find out they carry an EOFAD genetic mutation experience increased depression and anxiety immediately and up to 3 months following testing. In the same studies, however, depression and anxiety levels seemed to return to normal (or what the researchers call “baseline”) one year after testing. Therefore, for some people, results (whether they come back as positive or negative) can serve as a relief in eliminating uncertainty. Again, individuals may find clarity in their genetic testing results about whether to join a clinical trial, make lifestyle changes, retire early, have a baby, among other possible decision-making choices. For others, finding out their results can be an enormous emotional burden to carry. Some find it difficult to face a disease with no standardized treatment or cure currently available (Paulsen et al., 2013). Although these results provide evidence that individuals can return to their “normal” depression/anxiety levels one year following testing, it should be noted that no studies exist following the long-term psychological impact of genetic testing. It should also be noted that these studies only include data on individuals who have gone through recommended genetic counseling protocols and who have given considerable thought to their testing.

From conversations with fellow Youngtimers who are at-risk of inheriting EOFAD and who have not gone on to get tested, we’ve recognized common characteristics, including that these individuals tend to avoid thinking about the disease and that their hope relies in not knowing about their future with the disease. There is no right or wrong way to feel about getting tested.

Additionally, there is some risk for stigmatization or even possibly discrimination if you test positive (or have an EOFAD mutation).

People who find out that they will not develop EOFAD (because they test negative and do not have an EOFAD mutation) may experience survivor’s guilt. This means that they feel guilty that their family members have or will have the disease when they will not.  Many people with survivor’s guilt eventually find ways to funnel their emotions into something positive such as advocating for their community.

What are the benefits and drawbacks of predictive genetic testing for EOFAD? 

The decision to pursue predictive genetic testing is your choice. It is important to remember that genetic testing is a decision that only you have the right to make for yourself.

This is a difficult, complex, and very personal decision. No one besides you can truly make this decision for you. There is evidence that being influenced by others may result in having negative psychological responses to test results. Therefore, it is important to take as much time as you need to determine whether genetic testing is right for you. 

We recommend that you consider your personal goals and circumstances to help decide if genetic testing is right for you.  Factors like your personality, the type and timing of important life decisions, existence of other medical or mental health issues, and the nature of relationship with family members are all something to consider throughout your decision-making process. Even if genetic testing for EOFAD is medically appropriate, it isn’t required and you shouldn’t feel pressured to pursue it now, or ever. It is important to keep in mind that meeting with a genetic counselor does not mean you have to move forward with genetic testing. You can stop and decide it’s not right for you at any point in the process.

Table 1, below, illustrates the common characteristics of people who do well and may not do well with genetic testing. It is meant to help determine what contributes to whether or not a person benefits from genetic testing for EOFAD. Information in this table is based on conversations with Jill Goldman , a leading expert in genetic counseling for neurodegenerative diseases, and fellow Youngtimers who have undergone predictive genetic testing. You may see attributes of yourself in these described characteristics. However, there is no exact formula to figure out who will benefit and who will not benefit from genetic testing.

Table 1: Common characteristics among those that do well vs. may not do well with genetic testing and genetic status disclosure.

Genetic counselors have said that individuals who go on to pursue testing and benefit from it tend to be those who have put a lot of work into understanding and coming to terms with the decision to test and the impact it will have on their life going forward. They have gone through the entire genetic testing protocol (to find out what this entails, go to Part 2 of the Youngtimers Genetic Testing Guide) and discussed their concerns with their genetic counselor at length, sometimes over multiple sessions.

Genetic counselors have also said that individuals who do not pursue testing or do not respond well to testing could be those with pre-existing psychological issues, such as clinical depression and/or anxiety. In addition, individuals who do not like to make future plans or who do not currently have an adequate support system outside of the genetic counselor or other medical professional, may not be ready to find out their genetic status.

How do I know if predictive genetic testing is right for me? 

If you are on the fence and feel like you are constantly changing your mind about testing, then it is probably best to wait and give yourself more time to become comfortable with a decision.

For some, it takes years of wrestling with the decision to come to a conclusive decision. For others, their decision was immediate. It may also be helpful to know that you are not alone; less than 20% of individuals with a family history of dominantly inherited neurological diseases decide to get genetic testing.

Image 2. The majority of individuals at risk of Huntington’s disease, an autosomal dominant neurodegenerative disease similar to EOFAD, do not undergo predictive genetic testing. (Source: Baig et al. 2016, European Journal of Human Genetics)

You might consider speaking with a psychologist or mental health professional who is specialized or has experience in treating people with a family history of a dominantly inherited disease. They may help determine whether you are emotionally ready for undertaking the testing process. If you are having trouble finding one, genetic counselors may be able to make some recommendations.

If you are still having a difficult time deciding whether genetic testing is right for you, Youngtimers can help. Listen and read the perspectives of others within our community about their genetic testing experience , ask a fellow Youngtimer in one of our support groups , contact us to be connected with an experienced Youngtimers ambassador, post a question to the DIAD Facebook group , or get connected to a genetic counselor .

What if I can’t decide about genetic testing?  

Paulsen JS, Nance M, Kim JI, Carlozzi NE, Panegyres PK, Erwin C, Goh A, McCusker E, Williams JK. (2013). A review of quality of life after predictive testing for and earlier identification of neurodegenerative diseases. Progress in neurobiology, 110, 2–28. doi:10.1016/j.pneurobio.2013.08.003.

Can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833259/

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