When Marty Reiswig learned he might be a carrier of the PSEN2—a rare early-onset Alzheimer's gene—he joined a clinical study to find out more.
As a college student, Marty Reiswig decided to take his girlfriend to a family reunion. After he noticed many of his relatives struggling with everyday tasks like pulling out a chair, Reiswig decided to take a closer look at his family’s history with early-onset Alzheimer’s. Eventually, he learned that his family is one of only 643 on Earth known to carry the PSEN2 gene, a rare early-onset gene that nearly guarantees its carriers will develop early-onset Alzheimer’s.
While Reiswig is now 40 years old and has not yet gotten tested to see if he carries the gene, he enrolled in the Dominantly Inherited Alzheimer Network study (DIAN study).
The longitudinal study follows individuals with dominantly inherited Alzheimer’s disease (DIAD), or those who have a parent or relative with one of the three early-onset Alzheimer’s genes (PSEN1, PSEN2 or APP) and a 50-percent chance of having the same gene mutation.
While the researchers cannot tell Reiswig his genetic status, he has learned a lot through participating in the study. For example, researchers found that those with the early-onset Alzheimer’s genes produce too much beta-amyloid and their bodies are unable to clear it. These findings suggest that if researchers discover a way to stop the overproduction of beta-amyloid, they may be able to prevent early-onset Alzheimer’s or slow its progression.
Being Patient spoke to Reiswig about his family’s history, what he has learned by participating in the DIAN study, and his hopes for the future.
A Genetic Predisposition to a Rare Form of Early-Onset Alzheimer’s
Being Patient: Only 643 families on Earth are known to have been impacted by the PSEN2 gene. Who has been impacted in your family and what does it mean to have this gene?
Marty Reiswig: My grandpa, Ralph, became symptomatic with early-onset Alzheimer’s in his mid-40s and he was dead by the year that I was born. My father has very few positive memories with his dad. He was very symptomatic by the time that my dad was only 8 years old. Early-onset Alzheimer’s can really change people and gives you a pretty rough personality at times, so, unfortunately, those are the memories my dad has of his father. My grandpa and his generation is kind of what raised the red flag. My grandpa had 13 siblings and of those 14 kids in that family, 10 of them ended up getting early-onset Alzheimer’s by the age of 50.
Being Patient: Researchers only learned about the early-onset genes in recent years. How did your family learn about their genetic predisposition to early-onset Alzheimer’s?
Marty Reiswig: My grandmother, who was married to Grandpa Ralph, was a determined, spitfire woman. She took him all over creation to try and find somebody who could tell her what was wrong with him. She got all kinds of bad diagnoses and advice; they simply didn’t understand early-onset Alzheimer’s at the time. My understanding of it is a strange story. I was raised far from my dad’s side of the family. We live in Colorado and most of them are in Oklahoma and Kansas, so as a kid, out of sight, out of mind, right? I just knew that Alzheimer’s ran in our family, but it was not a clear and present threat. In college, I decided to take my girlfriend to a family reunion and to meet these people. I had only seen them a couple of times in my life before that. We got there and pulled into a local pizza joint, said our hellos and a few minutes later, my uncle Roy and his family came into the pizza place. He reached for the back of his chair to sit down over, and over and over, then he was finally able to grasp it and pull it out, but when he went to sit down, he nearly fell. I didn’t understand and I looked around the table and I just saw fear, shock, anger and shame because everyone around the family table knew what was happening. We later went to the gymnasium and it was very evident that this was a massive problem. I took my girlfriend out for a walk that night and I told her, “If you want out of this relationship right now, I will understand.” Without skipping a beat, she said, “I’d rather have 30 good years with you than a lifetime with anyone else.” We’re married now. I’d be crazy not to marry her.
Being Patient: Researchers recently discovered three early-onset Alzheimer’s genes that severely elevate your risk of developing early-onset Alzheimer’s: PSEN1, PSEN2 and APP. How did you find out that your family was a carrier of PSEN2?
Marty Reiswig: At that family reunion, Alzheimer’s became a very real problem, but that was before the human genome was mapped in the late 90s. As science has progressed, followed our families and taken blood samples for the last couple of generations, they really dived into the human genome project and discovered we were carriers at that time. I was a young adult, married, and having kids, but my dad’s first cousin, who we call an ‘escapee’ since he’s in our family but didn’t get the gene mutation, lived long enough to be a caregiver for all kinds of people in his family, including younger people. He wrote a book chronicling our disease and the scientific developments at the time. At the back of the book, he referenced the DIAN study. We contacted them and learned at this time that this is not just something that’s hereditary. This is an actual gene mutation and each new generation has a 50/50 chance of receiving that gene mutation. If you get that gene mutation in our family, PSEN1 or PSEN2, you have a 99.5-percent chance of developing early-onset Alzheimer’s [in your 40s or 50s].
Deciding to Get Tested for the Early-Onset Alzheimer’s Gene
Being Patient: You’ve decided not to find out whether you carry the gene. Why not?
Marty Reiswig: If it was just me by myself on the planet, I would absolutely want to know, but it’s not. I’m married, I have kids and a mother who has dealt with her own husband having Alzheimer’s for the last 15 years. For now, there’s nothing more that I can do. I’m already involved in research, advocacy and doing everything I possibly can already, so I’m living as if I have it. I’m choosing to take vacations and to live with no regrets.
Right now, I’m deciding not to find out because I don’t need the rest of my family to bear a burden that we might not have to bear yet. As I get closer to my family’s age of onset, 45 or 47 years old, I’ll probably want to know to make sure I can put all of the insurances in place and take a wild trip around the world. But for now, Alzheimer’s is not stealing much joy, so why allow it to steal more than it is already? I’m 40 now.
Being Patient: Have you had any counseling knowing that you could develop early-onset Alzheimer’s and how has it changed your outlook on life?
Marty Reiswig: I have a casual relationship with a counselor right now. I only go and see her when I’m having a really tough time. It is most difficult when I’m visiting my father because I look at him and I’m sad for him and my mom, but then very quickly, I see myself and my own possible future. That’s scary and sad. I go see her on an as-needed basis. As far as how it’s changed my outlook, I know this is going to sound really strange and possibly made up, but it’s not.
Being faced with your own mortality on a regular basis is different than having a car accident where all of a sudden, your life flashes before your eyes, but you survive the car accident. I’m sure that changes your life, but being faced with this on a regular basis has made me stop and think about life much more intentionally, live with no regrets, and make good intentional choices with my time, energy and money.
The silver lining about all of this is that I think it’s made me a better person in a strange and morbid way. A very popular philosophy in the 1600s and 1700s that permeated the entire society, including its art, fiction and literature was called memento mori, and it means “Remember you will die.” If on a consistent basis, you remind yourself that you are going to pass away, it very quickly begs the questions “How are you going to live?”; “What are you living for?; and “Are you actually in congruence with yourself, your choices and your values?” In a strange way, it has positively impacted my life.
There’s a great Confucius quote that says, “We all have two lives. The second begins when you realize you only have one.” That hits the nail on the head. I’ve realized I only have one life. Not to belittle this in any way, but it’s a little different than getting a stage 4 cancer diagnosis because a). There’s no treatment that’s effective for early-onset Alzheimer’s; and b). It’s not right now because I’m not dying in the next four months. I can’t just quit my job and travel the world. I still have to get up every day, raise my kids and provide for my family. It has affected a day-in and day-out relationship with death that was tough at first but has turned into a healthy and positive relationship.
Getting Involved With Early-Onset Alzheimer’s Research
Being Patient: Can you tell us about the research study that you’re participating in?
Marty Reiswig: In the back of that book from my cousin, he mentioned the DIAN study. My brother and I decided to enroll. We were like the eighth and ninth people to join that study and now it’s 900 people worldwide that they are studying observationally. The observational study has been going on for nine years and the drug trial has been going on for five years. We’ll get results from that at the end of 2019 and are hoping to see some positive results. As for what they set out to learn in the observational study, they’ve actually exceeded their goals in what they wanted to learn and discover.
Much of what you and the population now know about the disease has been discovered from the DIAN observational study. The reason for that is that they can take our blood and we’ve each been doing spinal taps every year for all of these years; they also track our medications, lifestyle, brain scans and all kinds of things. A couple of key things that they have learned—and it’s why science is now focused on early detection and prevention—is from our cerebral spinal fluid. They discovered that our gene mutation causes our bodies to overproduce and not clear out the beta-amyloid protein in our cerebral spinal fluid that goes up into the brain and then gets cleared out. Everyone has a normal level of this. It’s like a sink. If you turn on a faucet and the sink drain works correctly, then you could just run that all day, every day and it wouldn’t overflow or cause any problems. That’s what the normal body does. Our gene mutation causes the faucet to be on too high because too much beta-amyloid is produced. But could we improve the clearing of it? Could we improve the drain or turn down the faucet?
It turns out that just because our gene mutation causes that elevated level of beta-amyloid, doesn’t mean that our disease is any different than the general population. Later on in life, people are having elevated levels of beta-amyloid and that protein is staying in the sink—the brain—too long, and it’s a sticky protein, so it folds, sticks and becomes those tangles that you see when you look at an Alzheimer’s brain under a scan. So that’s the technical side of it.
Lifestyle Changes to Prevent Early-Onset Alzheimer’s
Being Patient: Research has found that lifestyle changes can be made to help prevent cognitive decline. Have you made any lifestyle changes to improve your brain health?
Marty Reiswig: Lucky for me, I didn’t have to make a lot of large changes. I was practically born an athlete. I love physical exercise. A recent study included some of the DIAN findings as well and found that even among gene mutation carriers and the general population, 30 minutes per day of exercise, but not more than two hours per day, is the sweet spot that helps to keep the brain a little bit more clear of those plaques and tangles for longer. It’s really about staving off the disease and delaying it as much as possible.
On top of that, they’ve also learned that the brain continues to grow new synapses. If you learn a new language, an instrument or have a job that continues to keep you mentally stimulated, you are learning and creating new synapses. Dr. Bateman, the head of the DIAN study, likes to say that you’re expanding the bucket of synapses that Alzheimer’s will eventually want to start draining out. If you start with a small bucket, your Alzheimer’s will progress more quickly, but if you can have a big, active, healthy brain, Alzheimer’s can go a lot slower and delay those symptoms. I have a general ketogenic diet. What’s good for the heart is good for the brain. A good, healthy balanced diet, exercise and staying very active with your brain are three things that I’ve seen over and over that help delay the onset of the disease.
Being Patient: What would you tell your children about protecting their brain health or learning more about their genetic status?
Marty Reiswig: One of the most amazing things that I am part of is a very private Facebook group that we call the X-Men, or genetic mutants trying to save the world from Alzheimer’s. Something that comes up on a regular basis is how to speak to our children about this.
There’s a great correlation between our situation that’s very genetic and ALS. ALS is directly the same. It’s a 50/50 chance for everyone. With ALS, social workers have found that talking about it early, being open, honest and supportive benefits children. If you hold off, wait and act like it doesn’t exist, then suddenly drop this bomb on your kids that hey, by the way, now that you’re ready to have kids or are about to have a child, we have this gene mutation, it’s really damaging to the relationship. They feel like you’ve been lying to them all of these years. We have chosen, kind of like with the birds and the bees, to tell our kids what is age-appropriate, and not dwell on it, but honestly answer their questions as they come in. I think there’s a really sweet protection that children have in their brain to not think too deeply about things, and they don’t ever think that they’re going to be 40 or 50 years old. As they feel more and more inclined, we just want our kids to know we are an open book and we will tell you anything and everything you want to know to whatever level is appropriate for you today.
Being Patient: Did you have any conversations with your dad before he got Alzheimer’s disease about his family being impacted by early-onset Alzheimer’s?
Marty Reiswig: A little bit. My parents really chose to—and I don’t blame them because they had so much less information at the time—ignore it, have a good life and hope that it wouldn’t happen to them. I think not stressing about potentially developing the disease might be one of the reasons why my dad didn’t have symptoms until much later than most of his cousins. Most of his cousins got sick with early-onset Alzheimer’s around age 48 and then passed away at 55 or 56 years old. My dad’s still in a nursing home in the final stages at age 66. I think that was generally how they wanted to handle it so we didn’t talk much about it in my upbringing.
Being Patient: When you talk about participating in the DIAN study, how much information do you get back? Are you learning more about yourself and your cognitive abilities by participating in a trial?
Marty Reiswig: It is entirely double-blind, so technically, we get absolutely no feedback about how we’re doing. However, if you went for the same one-mile run every couple of months, even if you didn’t take a stopwatch, you would gradually know whether or not you’re doing well, and feel like, yeah I’m getting a little faster, or man, I’m getting slower and more sore. Because we are so regularly tested on things, I’m very aware and almost paranoid about whether I’m forgetting people’s names or my keys and things like that. We do not get any technical data back. Even at the end of the drug trial, when we find out about the effectiveness and safety of the drug, we won’t find out anything about us individually, just how the drug did.
Being Patient: Some people suggest they have a fog surrounding their brain and they can’t tell that it was there until it’s been lifted. Are you hyperaware of your cognition, and have you noticed any signs of decline caused by normal aging?
Marty Reiswig: My wife does a good job of counterbalancing my fears and telling me I’m just fine. I have the benefit of this longitudinal study. Every year, I fly out to St. Louis to go through this same battery of tests and each year, I don’t know if they remember that I ask, but I try to build a little rapport with the folks doing it. I ask them how I did each year. They never tell me, but I can still tell that I’m doing pretty well. I’m encouraged because sometimes they will give me feedback that I’m doing better than the vast majority of the regular population.
So even compared to them, as well as compared to myself, I think I’m pretty sharp still and I don’t think I have that foggy brain yet. But I am like you, I worry about it, and therefore, I see every little mistake. Now it’s worse because the other major thing that the longitudinal DIAN study has determined beyond a shadow of a doubt is that those plaques and tangles are developing in the Alzheimer’s brain 15–20 years before symptoms appear. Here I am at age 40 going, oh man, I forgot another appointment, or I can’t count that money as fast, or whatever. I do get a little paranoid.
Being Patient: Have any of your siblings or other family members looked into whether they have the early-onset Alzheimer’s gene?
Marty Reiswig: I have an older brother and he found out several years ago that he does not carry the gene mutation. So far, each year, when we have our “X-Men conferences” that I like to call them, I ask that very small group of people, how many of you have decided to find out your gene status? About half the room raises their hand. Every time I bring this up with the general population, I get three different groups of people: a large group that says they would absolutely want to know right away; other people who say they’d never want to know their status; and a small portion in the middle who are not certain. It’s a very personal and divisive decision because there are so many ramifications.
Being Patient: What are your hopes for the future?
Marty Reiswig: I get to speak to scientists and pharmaceutical companies at the conferences that I go to. I just got back from the World Dementia Council in London where they had me present my story. In that room of the very best minds on the planet, there is a very strong amount of hope and confidence that we will have a disease-altering treatment in the next 10 years, if not five years. That World Dementia Council was actually a follow-up from the G8 Alzheimer’s Summit that was in London just five years ago. All the G8 countries made a commitment to having a disease-altering treatment by the year 2025. I’m actually very hopeful. I believe this is an exciting time for early-onset Alzheimer’s and dementia research, and pharmaceuticals. I truly believe that even if we don’t have a treatment for me in the next 7–10 years, we will have a treatment for our children and their children.
This interview has been edited and condensed for length and clarity.