“My life feels like I am visiting in someone’s house and hear a grandfather’s clock ticking. I fight back by being in DIAN and speaking publicly. It’s the control I have over my genetic destiny.” Brian Whitney, 44.
“I’ve never before met another family who has the same problem.” At-risk daughter, 19.
Brian Whitney knows he has inherited a presenilin-2 mutation that has decimated his extended family for generations and now threatens him—and perhaps his 5-year-old daughter. With his parents, Whitney joined 99 other people from Australia, Canada, Colombia, Puerto Rico, the United Kingdom, and across the United States for a historic, face-to-face meeting of families of the Dominantly Inherited Alzheimer Network (DIAN). Held July 18 in Washington, D.C., in conjunction with the Alzheimer’s Association International Meeting, the Autosomal-Dominant AD (ADAD) Family Conference brought together participants who are certain they will become symptomatic with others who already are. People who have learned their genotype spent the day with people who have not. At-risk teenagers mingled with baby boomers who lost their spouses to ADAD and are now fighting to save the lives of their adult children. Also there were members of the Colombian pedigree with the PS-1 Paisa mutation that has inspired the Alzheimer’s Prevention Initiative (API), who have moved to the United States and plan to join DIAN.
This in-person meeting grew out of repeated requests from DIAN participants, said the network’s leader, Randy Bateman of Washington University, St. Louis. Since the DIAN observational study started in 2008, its participants and researchers have gradually gotten to know each other by way of teleconferences, Webinars, an online forum, and a Facebook group restricted largely to ADAD family members. Families planned the day with DIAN-TU (Trials Unit) staff members including Washington University’s Ellen Ziegemeier (email@example.com) and Alzheimer Association staff. The Colombian API project builds cohesion in similar ways, said Francisco Lopera of the University of Antioquia, who received a standing ovation at the ADAD Family Conference for his work. His project invites participating families for biannual research updates in July and to celebrate Christmas, drawing about 300 each time.
After a multilingual meet-and-greet the night before, the families settled in for a day of lectures and intensive talks with each other and with researchers within and outside of DIAN. They discussed how to handle their genetic risk. They grilled pharma scientists about why they haven’t produced a new AD drug in more than a decade. They made impassioned pleas that their symptomatic relatives get access to investigational drugs. They heard an update of the ongoing clinical DIAN-TU trial of solanezumab and gantenerumab. They exchanged tips on how to solve the practical and financial problems that arise when dementia strikes in the prime of life. They shared how they are dealing with their genetic test results. In telling their stories, family members brought pharma, academic, and regulatory scientists to tears.
By the end of the day, the information and emotion together created a collective sense of being part of something unique, of a movement larger than even autosomal-dominant AD itself. “In 2050, 135 million cases of Alzheimer’s disease are predicted worldwide unless we change the course of history. You are empowered to do that,” Jeffrey Cummings of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas told an energized audience. The families—whose children have become symptomatic since their parents in the 1990s helped discover APP and presenilin— broke into spontaneous applause when Cummings declared, “We cannot lose another generation to Alzheimer’s disease.”
The work of DIAN and its clinical trials unit, DIAN-TU, is drawing attention beyond the Alzheimer’s field. “You should be proud of what you have pulled off. I am stunned at what is being done in this area. It is cutting-edge, and it is the right thing to do,” said Janet Woodcock, who heads the center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA). “This is going to be big for other diseases, as well. The cancer field is watching what you are doing,” said Maria Isaac of the European Medicines Agency based in London. Throughout the five subsequent days of the AAIC, this family conference resonated in scientific sessions and hallway discussions.
This series summarizes selected presentations; paraphrased audience questions and answers by speakers or other DIAN researchers are interspersed throughout as Q&As. To respect the privacy of families, names of DIAN participants have been removed except for those few who already advocate publicly. Part 1 focuses on genetic testing for an autosomal-dominant gene, Part 2 on news about funding care and research. Part 3 features family stories and debate about the DIAN-TU trial; and a final story summarizes ADAD research results presented at AAIC itself.
The ADAD family day started around genetic testing. Meagan Cochran, a genetic counselor at the University of Alabama at Birmingham, said that in 2011 the American College of Medical Geneticists and the National Society for Genetic Counselors jointly issued guidelines to standardize predictive testing for Alzheimer’s disease (see Goldman et al., 2011). Before then, local practices varied, with some people finding out their genotype directly through a local physician and others going through a lengthy counseling protocol borrowed from Huntington’s disease (see Genetic Testing for Early Onset Familial AD). The guidelines emphasize the need for a structured process that involves genetic counseling, a multidisciplinary assessment to gauge the person’s ability to cope with knowing their genotype, and post-test counseling and follow-up. Cochran said building a long-term relationship with the family, and involving a support person who is not at risk in the process, has proven helpful to avoid depression or other bad outcomes of predictive testing.
Q: Why can’t I just get tested?
A: I am not trying to make you jump through hoops. There is a lot of value in this protocol. Having the multidisciplinary people involved empowers you to give truly informed consent. It is still your decision, but a much better-informed decision.
Q: Who pays for the test?
A: If you do not want insurance to have this information, you have to pay out-of-pocket or be part of a research study. The DIAN and DIAN-TU support some genetic testing.
Q: When should educating minors begin?
A: It is never too early to start talking to kids. If you don’t, then they know something is going on, but not what. Some kids think it is something they are doing wrong, especially with the personality changes in the affected. But don’t over-share. Do not do a one-time, sit-down, big family meeting that is stressful, but incorporate age-appropriate bits and pieces into the life course. Stop when you have answered a child’s question. Create a new normal.
Q: What age do you suggest for testing?
A: It depends on the person. Some 18-year-olds are mature about these things; some 25-year-olds are not. It is important to know if the family has spoken about it before. Also, what personality type are you? Are you Type A and plan everything? Then test earlier. Would knowing drive you crazy? Then don’t.
Even though a consensus framework to guide the process is now in place, ethical dilemmas crop up, Cochran said. For example, a mutation found in a very young adult who insists on testing will “out” a parent who may not wish to know. A grandson who pursues testing of a deceased grandmother’s autopsy tissue to determine whether there is a family mutation would raise the specter of autosomal-dominant inheritance for all her descendants.
During a breakout session, discussion about how to handle genetic information continued among 45 at-risk people. About 40 percent knew their gene status. The hour seemed too short for many, and avid conversation continued afterward. In the anonymous excerpts below, successive answers to a given question are from different people.
Q: When you knew, whom did you tell?
A: I told most people, including my boss. It helps me.
Q: My genetic counselor said by telling you burden people.
A: That is true. I did not tell my mom because she is a worrier and lives with us. She would second-guess my every sentence if she knew I had the gene.
A: You do burden people by essentially forcing them to give you more empathy. I thought long and hard about whom to tell, but those I did tell have become my closest support network.
Q: I don’t know my status. How did knowing affect those here who do?
A: I did it to stop the constant worrying. Now that I know I am positive, I still worry when I forget something, but I am glad I did it.
A: I found out for my family’s sake because I am my mom’s caregiver. Now I know our options and can plan. For me it’s better that way.
A: For me it was practical. I found out this year. Now I am thinking I may not be functioning in a decade, so should I really gun for this promotion? It changed how I live my remaining good years.
A: I passed up a higher-paying job that would have put me on the road and instead am spending more time with my family.
A: I am close to my family’s age at onset by now. We live abroad but decided to return home and live near our extended family so there is help when I become symptomatic.
Q: Does anyone here regret having found out? [Most heads shake, but ...]
A: It depends on the day. Some days I am blue and regret I brought a child into this risk.
A: No, but I strongly suggest getting genetic counseling. DIAN will find a counselor for you. I just looked up a geneticist and was in and out in 30 minutes. He asked: "Do you want to come back for the result or get a phone call?" I said a phone call. It was the most horrible pain. I was at work. My wife was not with me. I stood there and cried. No follow-up. For three years, I was up and down with depression and weight gain. I never spoke with a counselor. I just don’t reach out. I eventually got on an antidepressant and that helped. Don’t do it like this.
A: As a spouse, I say to those who are considering testing: Do not think only about tomorrow and planning. Think about today and how you will live. This can eat you up.
Q: Why not plan for the future without knowing? I can take out long-term care insurance, etc. I plan as if I am positive, and still live not knowing my status.
A: I hear you: Let me live in well-prepared, blissful ignorance. But I found it did not work for me. At one point I just had to know.
Q: I will find out at some point. But when?
A: You will know. I took care of my mom and she passed, and I still did not want to. Her death was life-changing, I went back to a new normal for some years, but then it came back and hit me. You will feel it when the time is right.
A: For me, it was starting to forget things. Every time that happened, it was, “OMG, I am getting AD!” I realized that either I will be a happy 50-year-old who knows AD is coming, or I’ll go crazy. That was it.
A: My wife would have to be a caregiver, so when our kids were in their teens it just felt right to find out.
Q: What’s it like for the people here who tested negative?
A: I feel a survivor’s guilt, but more in a sense of responsibility for the others, not as a psychological burden.
A: Knowing I do not have the gene helped me just pour love on my sister who died of it. My cousin has four children and they all have the gene. She had to provide for and take care of all four of them. She needs help from someone who understands.
A: My brother is negative. As someone who is positive, I am glad he found out because I can give him power of attorney.
A: Some of us are getting tested solely for our children because they are hitting 18 and want to know.
A: In our family, onset is 35. I was past that but chose to get tested because my 23- year-old was talking about having kids. I said let me get tested so maybe you do not have to. I was negative, but my three siblings all have it. I am relieved for her, but it’s still complicated.
A: My dad was 47 when he died but it was never talked about. So when my sister got it, it took us five years of diagnosis to find out what she had. Taking care of her, my nephew, my niece, is almost more than I can bear. I do it because I love them, and I can do it because I don’t have the gene. —Gabrielle Strobel
- At DIAN Family Meeting, Funding News Caps Talk of Inadequate Services
- Families Challenge DIAN Scientists to Do Even More, Faster
- New Data on Autosomal-Dominant Alzheimer’s Point to Early Fissures in the Brain’s Microarchitecture
Book page Citations
- Goldman JS, Hahn SE, Catania JW, Larusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, Bird T, . Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011 Jun;13(6):597-605. PubMed.
No Available Further Reading