Families participating in the Dominantly Inherited Alzheimer Network (DIAN) made an impassioned case for pressing on with clinical trials at two recent gatherings of the network. Speaking to a hushed audience, their stories drove home the brutal reality of autosomal-dominant Alzheimer’s in 2012: A quarter century after their affected mothers, fathers, aunts and uncles cracked open the molecular biology of Alzheimer’s thanks to their research participation, their own generation is now dying and younger relatives are again growing up with the specter of early onset AD hanging over their lives. In the intervening years, research has flourished and initiatives such as DIAN and API are going full steam, but on the bottom line—therapies to prevent those long, slow deaths—nothing has changed yet. Sons and daughters are still getting sick in mid-life just as their parents had before them. At the 8th Leonard Berg Symposium, held on September 28th at Washington University, St. Louis, three relatives in their 30s and 40s from two families spoke to an audience of 370 assembled scientists, fellow families, and other stakeholders about what being in DIAN means to them. Another family had addressed DIAN’s Pharma Consortium at its previous gathering last July in Vancouver, Canada.
In 2012, a growing number of relatives are open about the disease among friends and even on TV and radio. Others cannot bring themselves to confront the fear, much less join DIAN. For the first time, however, these relatives are now hearing of a preclinical treatment trial (see Part 1 of this series), and that is changing minds. “For years I used to be the one who called my siblings and cousins about DIAN and got no replies,” said one participant who requested anonymity. “Now I am getting calls from them.” Below are excerpts of what the relatives told the scientists, edited for clarity.
Rachel Huber, Iowa
“I will never forget the evening when dad decided to retire. I was 14 and did not know what Alzheimer’s disease meant, but after dad’s diagnosis, life changed. My role shifted toward having more responsibility. My sister was six then. She watched over dad more than a six-year-old should.
“Dad died slowly. He used a bike, then walked, and we supervised him. It became harder to be social with him. We stayed with him and kept him safe. We fed him when he could not anymore.
“My husband and I spoke about Alzheimer’s before we got married. We chose to have a family and now have two young daughters. The possibility of getting it is the invisible elephant in our lives. It is always there.
“When I was a mother my perspective changed. Two first cousins have died of AD, one was 50, one was 42. It hit me then that we have to find a treatment before this goes on to another generation.
“I am amazed about the amount of knowledge about AD nowadays and the ability to diagnose it better since I was in high school. To become involved in DIAN has become a blessing. I have been part of his progress, and feel comfort that so many others do the same thing. I now see so much hope for our children.
“I find the DIAN procedures tolerable. But for the upcoming treatment trials, I have one request. I would like there to be a compassionate clause where if someone does progress to symptoms, he or she is unblinded and switched to drug.
Joe Heinrichs, Iowa
“I am the oldest of six children and father of three boys. My oldest memory of AD is my grandma. With dad, my earliest memory is working on the cellar stairs with him and asking mom: why does dad keep asking the same question over and over?
“Shortly after dad was diagnosed, mom and dad had us meet with a doctor and counselors. He told us that we should not have children. His cure was to wipe out our line. I don’t want to know if I have the gene. If I knew I had it, I would not have gotten married and had children. I also do not want to know because this way I don’t care whether I am on placebo. I don’t like the need for placebo but I understand it.
“From the beginning, dad took part in any and all research programs he could find. We take part in DIAN because he would have, and because we expect you to find the cure. Perhaps not for us, but certainly for our children.
“The burden of taking part in the tests is not an issue for us. The psychometric testing is hardest, actually. And honestly, the 24-hour spinal tap I took was not fun. But that does not matter. Dad did those things for us. As far as the time and emotional toll of being in DIAN, it is just part of dealing with AD.
“Science has made so many strides that I have hope that you will find a cure. Some of you may do it for personal reasons; some may expect a big payday. I accept both reasons. I just do hope you find the cure.
“I am the caregiver of my affected mother. She lives with my three sons and me. I also work full time as assistant school principal.
“We are the reluctant family. The Heinrichs and my family have much in common. One thing we do not share is that they have been able to contribute a large number of participants to DIAN and that is not the case for us.
“Three years ago I addressed an audience here during the 2009 Leonard Berg symposium (see ARF related news story). I was not sure then what this DIAN study was going to accomplish but it sounded good. I went home and told everyone about it. My siblings and cousins expressed enthusiasm, but three years later you are still looking at recruit number 1 and only.
“Why do they not join? Some of my cousins actually have AD; some relatives fear it to the point of paranoia; some live very busy lives. There are language barriers. There are cultural barriers. We are a Puerto Rican family. Then there are the fears about confidentiality, insurance, impact on jobs and, yes, the ever-present elephant-in-the-room kind of fear.
“It is true that going through the testing protocol brings all these thoughts up. Many in my family have worked all their lives to avoid these thoughts because we want to live as normal lives as possible.
“There is the perpetual heartache of this disease striking generation after generation. We all continue to suffer the same pain over and over. And at the core we all want the same thing: to break free of the chains that bind us to this disease.
“Hopefully once the trial starts, my family’s reluctance will change.
[Editor’s note: This address was made on 28 September. On 10 October, the DIAN clinical trial was announced. That week, the family’s second member joined DIAN.]
Ione Whitney, Seattle
“My husband Doug was 10 years old in 1959 when the 14 Reiswig siblings sat for a family picture. Six of them, including Doug’s mother Mildred, died of Alzheimer’s in their fifties, three in their sixties, and one at 71.
“In 1963 Doug’s Aunt Ester May took her husband to doctors to find out what was happening to him and his siblings. Many in the family did not want to discuss the diagnosis he got—Alzheimer’s. Most pulled back to their own family units and dealt with the disease by themselves.
“In 1968 Doug joined the Navy. In 1971, when I was pregnant with Brian, we received a letter telling us the Alzheimer’s might be hereditary. On a family visit that Thanksgiving, Mildred couldn’t remember how to make pumpkin pie. I didn’t think it was a big deal but Doug and his siblings knew it was the start.
“In September 1972 we took Brian to meet grandma. She had started leaving the house and getting lost. When we returned 2 years later from our station in Spain, Mildred mostly sat and stared into space. She held her new granddaughter, Karen, but didn’t know who she was. In October 1976 we visited again before heading to our new duty station in Hawaii. With her death three days later, at 55, we knew we would now wait for this to hit the next generation.
“In those intervening years, every time Alzheimer’s was in the news we rushed to hear. In the mid-1970s, research blamed aluminum. No more cans, no aluminum cooking pots. Later that was disproven. Around 1980, we received a letter saying that since the Reiswig family was so intelligent, was it possible that they were burning up brain cells and this was causing Alzheimer’s? Seemed illogical but Doug and I talked about it. Several weeks later Brian’s teacher called to ask why the boy wasn’t doing his work. It turned out Brian had overheard us and he knew his grandmother had died from Alzheimer’s, so decided if he wasn’t smart he wouldn’t die.
“Aunt Ester May connected with Drs. Thomas Bird, in Seattle, Washington, and Gary Miner of Tulsa, Oklahoma; in the mid-1980s and in the early 1990s; all of Doug’s siblings participated in a study. In 1995 the New York Times ran an article titled THIRD GENE Tied to Early Onset Alzheimer's, PS2 Volga German gene on chromosome 1. This was our family they were talking about! Does that mean we are on the way to figuring out this horrid disease?
“Through the years we heard that this aunt or that uncle had died. Now we are hearing about the next generation. Doug’s oldest brother, Roger, started showing signs when he was in his late 40’s. He was just several years older than Doug, so for years the kids would ask, “So, what has Dad done or forgotten?” But nothing happened. In 2001 Roger died at 55. When Doug turned 60 we figured he had won the coin toss.
We became friends with Doug’s cousin, Chuck Jackson, and have watched his struggle with the disease. He was diagnosed at age 50 in 2004. He testified before Congress with his battle cry “We will not go quietly to our graves.” [Listen to Jackson on StoryCorps in 2007.] By now, Chuck no longer speaks. Doug’s cousin Gary Reiswig wrote the book “The Thousand Mile Stare (see Alzforum book review.)” Gary asked Doug to consider DIAN. Even if Doug did not have the mutation, Roger’s three boys would be at risk, and many cousins and their children. Gina Kolata from the New York Times followed Doug through the testing and wrote an article in June, 2012. When we came home from St. Louis, Doug decided to find out his genetic status so that Brian and Karen would not have to worry. Brian and his wife, Andrea, had our granddaughter, Emily, who was just turning 1. To our shock, Doug tested positive. He had just turned 62.
This put Brian and Karen back at risk. Some months later, they were in St. Louis. They agreed to let CBS Early Show follow them through their DIAN testing and the segment aired in October 2011. Newspapers have written about us, too (e.g., see Kitsap Sun article). Both Karen and Brian chose to find out their mutation status.
Once Doug had joined DIAN we had hope. As he shared this hope with family, siblings joined. So did Roger’s son Brent. Brent found out that he has the mutation. He is 32. Brent called Tulsa 6 television station and offered them an interview. Brent and his second cousin Matt, who is also in DIAN, were interviewed; that piece aired in July (KOTV News clip). To me it is amazing to hear hope in these young people’s voices. Someone said, “Brent keeps talking about the DIAN study and the drug testing. He’s obsessed.” No, not obsessed: he is fighting for his life. In the interview he said, “Most people think of middle age as 50. I passed middle age at 25.”
As you start testing therapies, consider the statistics below for the five generations of our family who have been part of Alzheimer’s studies for 25 years:
- Generation 1: 14 Reiswig siblings, 10 died of AD.
- Generation 2 (Doug’s): 36 children. As of 2012, 25 at risk, five have died in their fifties and sixties.
- Generation 3 (Brian and Karen’s): 87 grandchildren. As of 2012, 44 at risk. Three had genetic testing, one negative, two positive, one already showing signs.
- Generation 4 (Emily’s): 46 great grandchildren. As of 2012, six at risk, one confirmed. Additional ones currently estranged.
- Generation 5: one great-great-grandchild so far at risk.
The photography editor for the New York Times asked for multi-generational pictures. When the elders in your family die by 60, there aren’t any.—Gabrielle Strobel.
- St. Louis: The Family View—What Do Study Volunteers Want From DIAN?
- ARF Notable Book: <i>The Thousand Mile Stare</i>, by Gary Reiswig
- Expanding the Network, DIAN Starts Showing Longitudinal Data
- Data in Disguise: As Results Roll In, DIAN Works to Guard Privacy
No Available Further Reading