“One day you will tell your story of how you’ve overcome what you are going through now, and it will become part of someone else’s survival guide.” Luciana, 29, DIAN participant.
“The disease might lie inside us, but so does the cure.” This line from Lindsay, a 23-year-old college graduate, captured the mood in the room when 263 people from 15 countries gathered for a day of news, commiseration, and a reinforced commitment to solving the problem of Alzheimer’s disease. On July 13, the day before the Alzheimer’s Association International Conference began, 139 sons, daughters, mothers, and fathers from families affected with dominantly inherited mutations in the APP or presenilin genes traveled to Los Angeles to meet with 124 researchers and staff in academia, pharma companies, the association, and the National Institute on Aging, including its director, Richard Hodes.
- New people at risk of dominantly inherited AD keep joining DIAN.
- Participants number 562; they live in eight countries on five continents.
- Millennials prepare for first primary prevention trial.
The meeting offered a mix of science and family news. Researchers presented science updates on the Dominantly Inherited Alzheimer’s Network observational study (DIAN-Obs), which started recruiting its first members in 2009. In particular, Alison Goate of the Icahn School of Medicine, Mount Sinai, New York, summarized what nearly 30 years of studying familial AD genes has taught scientists (see Part 2 of this series). Tim Miller of Washington University, St. Louis, explained a genetic therapy that may be coming down the pike for DIAN families, and panels of scientists from within and outside of DIAN research fielded audience questions (Part 3). WashU’s Randy Bateman reviewed how far the clinical trials platform DIAN-TU has come since its inception in 2012, and WashU’s Eric McDade polled family members about how best to handle questions of pregnancy in a primary prevention trial in people 18 and older that is ready to enroll (Part 4).
For their part, the families displayed a deepening bond among those who have come to these annual meetings since the inaugural one in Washington, D.C , which drew 100 people (Aug 2015 conference news). Connected by their shared experience and DIAN, Millennials from Japan are becoming friends with others from the Netherlands, the U.S., and elsewhere. In LA, DIAN families initiated first-timers, one of whom said: “Finally, I am meeting people who understand how I feel.” They missed previous attendees, such as Dean, Ted (last names withheld to protect family privacy), and others, whose advancing disease and work commitments kept them kept them home this year.
In 2008, when the DIAN initiative was first funded, there was widespread doubt that the network would draw enough participants to achieve its goal of recruiting 240 participants into an observational cohort. Ten years in, the overall network stands at 562 between its observational cohort and its trials unit, DIAN-TU. DIAN researchers and staff increasingly use a registry as a channel not only for recruitment but also for communication with existing participants, issuing newsletters through it as well as calls to help try out new cognitive tests and answer survey questions.
The audience at this family conference marveled at how new people around the world keep coming forward and take initiative. In Los Angeles, four family members addressed the audience. Below are edited excerpts from three of them; Alzforum withheld last names and hometowns to avoid accidental identification of their families.
“Dear Alzheimer’s scientists, please see beyond the stoic mask we present to you. See our anger, sadness, fear. Our families have been torn apart.
“Mine is a Catholic family of six. We grew up in the ’60s and ’70s with sports, school, road trips, friends, and family. In 2005 my dad started showing symptoms. He was diagnosed and died in 2013. Around that time, though, my two older brothers showed symptoms, too. That was the start of a journey of understanding, acceptance, action. My brother learned about DIAN and went to the Columbia University site, but still I did not know how our disease was genetic. I just thought it ‘ran in families.’ When a cousin told me I had a 50:50 chance, I joined DIAN.
“I faced big decisions: Do I get tested? Do I find out the result? I decided right away. Now we know four of us carry the mutation, I don’t, one is unknown.
“I’ve been devastated by survivor’s guilt. I feel huge gratitude that I do not have to face the day-to-day degradation of my life, but have been wracked with the question of why I am not a carrier. I know the answer now: so that I can help my siblings. We had a family conference to decide what to do about it. I had plans, now I do this.
“We use humor to take the sting out of the chaos of 24/7 care. It is easy to get paralyzed by fear. Please have the courage to ask for help.”
“My mom was 50 when her symptoms appeared. Now she is 69, still at home, but has been bedridden for the last nine years. I am the youngest of five, and eight years younger than my closest sibling. I was 10 when her symptoms started. Growing up was hard, as I was watching my mom forget the things about life that I needed to learn. She used to be a magnificent math teacher, but couldn’t solve problems any more. She was losing the ability to cook, to write, to talk, and now even to walk and eat. Everything related to my life as a teenager—school, friends, boyfriend—I talked about with my father, who also took care of her. He passed away last December, leaving a huge hole in my heart. I don’t understand why life is so hard.
“Mom’s diagnosis was uncertain until a few years ago. In 2012, her sister died with similar symptoms and, together with my grandmother’s cause of death, made me distrust my mom’s initial diagnosis. My daughter was a baby and I began to fear the future. I did not want her to go through the same thing. I needed to find out what was going on. So I started to dig.
“It took me three years to piece together a family tree with 80 members across six generations. Nobody had done that before. As I am the youngest in my generation, some relatives had passed away long ago and it was difficult to find old people to talk to. Only a few provided data. I contacted distant relatives, introduced myself, and asked about neurological symptoms in them and their elders. I begged them to forgive that I was making them remember a painful past. I traveled to other provinces in Argentina, sat down with relatives there, and asked them about our relations. Then there was Susana, my mom’s cousin. I found her telephone number on the internet and called her. 'Are you Susana?' 'Yes.' 'Are you a daughter of Claudio?' 'Yes. Who are you?!' On our second phone call a year later, I realized Susana was symptomatic. Two years ago, she died. Her sister died at 49, of dementia. [Editor’s note: names changed to protect anonymity.]
“I visited hospitals, civil registries, and cemeteries to get dates, names, and causes of death. They were reasons like ‘psychological problem’ or ‘madness.’ In the pedigree, it looked as if the disease started near a great-grandfather, who was Lebanese. He arrived in Argentina at the beginning of the 20th century, where he raised four children, all of whom seem to have died young of dementia. I was able to get his death certificate and realized he died at age 51 in a psychiatric hospital. That made me think our family mutation came from Lebanon. I traveled there. I met family and got information about relatives, but nothing about the disease. So I believe he may have had the founder mutation.
“I took the pedigree to other doctors and showed them that my mom’s disease was not ‘just’ dementia. They ran a genetic test and found a mutation in PSEN1. The truth was devastating and a relief. If anyone in my family gets symptoms, we can know why and won’t have to start at the beginning.
“I felt responsible for others in my family who could be affected. But how would they react if I told them this sensitive information? I asked them first if they wanted to know our family’s genetic result, without saying that I already knew it. This way they could choose. Some did not want to know, others did but did not want to test themselves. I believe having information gives us power and opportunity; not having information leaves us unprotected and vulnerable.
“I hope my story encourages you. We are on the right path and an active part of the solution. All of you are now part of my extended family.”
“I am 23, and recently graduated from a university in Ontario. I’ll tell you how I chose to cope with my family’s Alzheimer’s disease. In eighth grade, I wanted to become a pharmacologist and find a cure for Alzheimer’s because I was watching it take my nana away
“Six of the nine siblings in my grandmother’s family had early onset AD. My dad showed symptoms at 44 and tested positive for a presenilin 1 mutation. I learned this the summer I left for university to study pharmacology. He is in the solanezumab arm of the DIAN-TU trial. He attended the family conference in London in 2017, but cannot travel anymore.
“At college, I joined my university’s AD society, raising money and educating peers about genetic forms of AD. Now I am on the board of Youngtimers, a nonprofit online resource some of us are building for young adults affected by this disease.
“My brother and I got life insurance, but are holding off on genetic testing. There is no DIAN-Obs site in Canada, and while there is a DIAN-TU site in Toronto, we are both too young for the DIAN-TU arms 1 and 2 that are finishing now. But we are in the right age bracket—above 18 and more than 15 years younger than the family age of onset—for the primary prevention trial that is starting up next year. I will be in that trial, 100 percent.
“When you join the primary prevention trial, you can’t get pregnant because it’s not known what the drug might do to a fetus. It’s extremely important to complete this trial and avoid drop-out, but by the time it’s done I will be at least 30. So I chose a fertility clinic as part of the internship requirements of my university programs. Working there helped me investigate freezing of my eggs, and also in vitro-fertilization, as a way to protect my ability to have children. I am in the middle of the process. I have finished the diagnostics, am taking supplements to improve the quality of my eggs, and this fall will take the necessary hormones and undergo the egg removal procedure.
“Choosing to freeze my eggs is one of the biggest decisions I made in life so far. It was a personal choice. I get anxious before the appointments, and it is expensive. [Editor’s note: in the U.S., egg freezing costs up to $20,000, plus an annual storage fee. Some employee benefits and health insurance policies may cover parts of it].
“Storing my eggs gives me a sense of control over this disease. And if I find out later that I carry the mutation, then I’ll have the option of preimplantation genetic diagnosis (Jul 2014 news series). Knowing how can protect my fertility while participating in PPT gives me comfort.
“When I graduated, it meant the world to me to have dad watch me walk across the stage, whether or not he understood what was happening. My goals have changed since eighth grade. I will be a pediatrician, not a pharmacologist. But I am still determined to help find a cure for AD. I will just do it through research participation instead.”
Lindsay and other family members, including Doug and Ione Whitney (from the Reiswig pedigree afflicted with a presenilin 2 mutation, see 2010 book review), were seen throughout the main AAIC conference that immediately followed the family meeting. For an update of genetics research in DIAN, see Part 2.—Framed and edited by Gabrielle Strobel
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No Available Further Reading