Site Content

July 2024

We are having wonderful conversations with potential i-Forget participants as we ramp up to undertake our pilot research study. After the many insightful questions we've received during those calls, we wanted to share our responses with the broader i-Forget community and other potential participants. So, we sat down with our research director, Dr. Brent Zanke, for a Q&A.

My professional background is in medicine and genetics. After graduating with a medical degree from the University of Manitoba in 1983, I did a subspecialty in oncology, followed by a genetics PhD. My driving interest was in cancer epidemiology from a genetics perspective. I wanted to explore the relationships between what causes cancer, treatment outcomes and inherited genetic differences. 

I became interested in Alzheimer's disease for a couple of reasons. One, it's a hot area of research right now, and likely to be one of the defining illnesses of our time as our population ages. Also, my mother lived with cognitive decline before she died, so I've seen the heartbreaking effects firsthand. The critical and precious possibility of preserving brain health inspired the launch of the i-Forget research study.

For most of medical history, we've ignored the contents of our intestines. The exceptions are a couple of conditions, like food poisoning and, more recently, peptic ulcer disease and the bacteria associated with them. But over the last decade, we have learned that the gut seems to play a much bigger role within other body systems than we understood.

We are just starting to define the thousands of molecules made by intestinal bacteria, which are found unbelievably in our blood, and their role in things like inflammation and aging. Inflammation is the body's natural response to injuries and invaders like germs and helps us heal. But sometimes, inflammation happens without injury or an invader, which can be harmful and result in disease. Researchers have uncovered that as we get older, we experience more chronic inflammation, potentially influenced by what's living in our intestines. Animal studies, for example, have shown gut bacteria changes in models of neurodegenerative diseases such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease. What we don't know yet is how to use these findings to prevent these health conditions.

So, the research community is excited about purposefully changing the microbiome (the term we use to describe the microorganisms in a specific area of the body) to change the course of chronic disease and aging.

This area of research is still very new, and we are hopeful that the i-Forget research study could contribute to our understanding of what's at play in Alzheimer's disease.

Generally speaking, there is interaction between our genetics and our environment when it comes to disease. But the amount each plays a role varies. In some diseases, genetics are critically important, while in others, environmental factors such as lifestyle are more important. Genetics often play a role in childhood diseases, whereas the environment has a more significant role as we age. Environmental factors like cigarette smoking, exercise, and diet might combine with genetics to influence disease.

We're learning that people with specific genetic variations also have different intestinal microbial contents. For example, the intestinal microbial content in people who can't digest lactose (a sugar found in dairy products) differs from that of people who can. There is also a genetic component to the condition.

So, what's the Alzheimer’s connection? That's what the i-Forget study is trying to explore. Alzheimer's disease has a clear genetic component. Let's find out if specific microbes are also involved.

Well, there are ways to change an individual's genes through gene therapy, and several products are in development to do just that. But they are very expensive, and we don't know if we would be able to specifically repair the genes associated with Alzheimer's disease.

Is it possible to change the microbes in your gut? Yes, and it's being done now to address other diseases. Technologies are available to engineer bacteria and alter the microbiome's composition. From a genetics perspective, I think we will likely see intestinal therapies rather than changing an individual's inherited genetics.

With the i-Forget research study, we are trying to identify the target bacteria to aid the next generation of intestinal therapeutics. In the future, researchers might uncover how to introduce a helpful bacterium to compete against the particular microbe involved in setting off the sequence of developing Alzheimer's disease in those with genetic risk.

No, it doesn't. One of the gene variants involved in Alzheimer's disease is called APOE4. If you have two copies of this gene, you have a ten-fold increased risk of getting the disease sometime in your lifetime.

That leads to the question, why doesn't everyone with this gene variation get the disease? Recently, researchers have identified variants of the APOE4 gene that seem to lessen the negative effects of having two copies of the gene. Genetics is complex, and “genes are not destiny.” 

Lifestyle and environmental factors could also be involved in human disease that can lessen the effects of genetics. Take heart disease, for example. A hereditary predisposition can be countered by exercise and eating a heart-healthy diet. These actions can lower your risk significantly. On the other hand, there are always outlier examples of people who seem to do everything "right" and still get the disease and others who do all the "wrong" things and don't get the disease. These examples clearly mean we don't yet understand all the factors involved in genetics and disease.

There is much ongoing research regarding prevention strategies, such as taking specific probiotics. Probiotics are foods or supplements that contain live microorganisms intended to improve the good bacteria in your gut. But, we still need validation studies on these approaches that confirm they are effective or point to ways to improve this kind of intervention. A probiotic “shotgun” approach could just as easily be harmful as beneficial. 

There are other diseases related to brain health that can increase the risk of dementia, such as vascular disease and diabetes. Early diagnosis and treatment of these conditions could lower your overall risk.

Measures that everyone can undertake regardless of genetic risk can help preserve brain health. One hypothesis is that keeping our brains sharp and functioning optimally can provide us with "cognitive reserve" so that even if we suffer some decline, we can still function at a higher level for longer.  

General lifestyle advice that is familiar to most people can help promote healthy aging. Eat a balanced diet, don't smoke, exercise, and limit drinking alcohol.

It could. The term pharmaceutical is evolving. Traditionally, the term applies to drugs made from small organic molecules that we use to treat particular health conditions. Over the past couple of decades, we have increasingly seen biological medical interventions. So, instead of a chemically synthesized drug, we are seeing naturally occurring molecules manufactured at scale that are therapeutic in some people. Insulin to treat diabetes is an example of a biologic intervention.

Some day, intestinal gene therapies or the infusion of specific helpful bacteria might be possible to treat medical conditions, including Alzheimer's disease. This type of biotherapy might target someone's specific genetic predisposition.

None of that is possible, though, unless you know where to look and can identify the abnormalities in the gut microbiome. So, the goal of the i-Forget research study is to provide a kind of altas of genetic and microbial pathology that could provide a roadmap for the type of interventions we need to design.

Our model is unique, and we're confident it will transform the way we undertake big data and big science all over the world. To fund the i-Forget research study, we created a charity organization called The Durable Mind Collective. Our organization's mandate is to make our valuable study data commercially available to academic and other researchers. Any resulting revenue will go towards our charity. The aim is that this revenue, alongside traditional fundraising, will make our charity self-sustaining—enabling other research studies.

Three things have made this model possible today. One is that crowdsourcing research participants has become much easier via social media and other digital platforms. Second, genetic testing costs have decreased significantly, so running large studies doesn't require a huge budget. And third, artificial intelligence and other technologies make data analytics much faster and more accessible.

Another unique aspect of our model is that we consider our participants a philanthropic community. Their contributions to the data will directly support the commercial value that will fuel further research. In this way, we see our participants as collaborators.