Interview conducted by Emily Henderson, B.Sc.

News-Medical speaks to Dr. Keith Fargo from the Alzheimer’s association about their latest research which looked at risk factors that could aid in the early detection of Alzheimer’s disease.
Why is it important to research Alzheimer’s and its risk factors?
Alzheimer’s is a huge problem.

It is a fatal disease, which a lot of people might not recognize. People think of it asalmost like amnesia or normal cognitive decline that you experience with aging. But it is not.

It is a fatal brain disease and it is extraordinarily prevalent. When you look at people who are over the age of 65, about 1 in 10 individuals suffer from Alzheimer’s disease. In people who are over the age of 85, it is about 1 in 3.

Therefore, this is a major killer and an important, but an unfortunate cause of death. If we can get a handle on this, we can save lives.

What are the risk factors for the early detection of Alzheimer’s?
I think that some of the most important risk factors for Alzheimer’s disease have to do with genetics. There are some genes that can cause people to develop Alzheimer’s with certainty. There are some other genes (APOE e4) that increase the risk for Alzheimer’s quite dramatically. However, we, unfortunately, cannot change those genetic risk factors.

It is important for us to understand the risk factors that are modifiable. When you look at the modifiable risk factors, the best estimate right now comes from The Lancet Commission on Dementia and according to them, you could prevent up to 40% of dementia cases worldwide just through having an impact on modifiable risk factors. These factors include; education, sedentary lifestyle, poor dietary habits, cardiovascular risk factors, etc.

What research led to the discovery that these risk factors could be seen as young as teens and early 20s?
We have not seen this kind of work before this year at the Alzheimer’s Association International Conference, AAIC, where we saw a report and I believe it was specifically focused on BMI.

They studied a number of people who had information about their early life, BMI and cardiovascular risk factors, diabetes, et cetera. It found that the people who had multiple cardiovascular risk factors, even before they became adults, those individuals had a much higher risk for developing dementia later.

Now, this is really intriguing to the field because we know of course that in Western countries, we are seeing increasing rates of obesity and even increasing rates of childhood diabetes, so that gives us some concern for the future prevalence of dementia as these people begin to enter the age of increased risk.

I think that it also helps from a public health perspective to understand where to put our resources to have the greatest impact on dementia risk. It is interesting and probably somewhat fortunate, that some of the risk factors for dementia are very similar to, or identical to, the risk factors for stroke and heart attack.

Why is the risk of Alzheimer’s higher in African American individuals?
That is a wonderful question and it is a very important question as well. When you look, at least in the United States, we do find that risk for Alzheimer’s and other dementia is higher among underrepresented groups.

In the United States, we know that dementia risk is about double for African Americans as it is for Americans of European ancestry, and for Latin Americans, it is about one and a half times as high as it is for Americans of European ancestry.

Therefore, it is really important for us to understand why that might be as we are developing new approaches to risk reduction. Also, we are looking for new potential medications, so we have to understand that these are going to be effective for everyone, not just certain populations.

We struggle in the US and I am sure others do around the world as well, to get representative samples for some of our studies. Therefore, we need to do a better job of making sure that we are studying everyone, in particular, those who are at increased risk.

In terms of why African Americans at increased risk, it can be difficult to study. But so far, the studies we have seen almost universally suggest that the most important factors are life stressors.

For example, if you turned 75 today, you were born in 1945, and we, of course, know that discrimination and systemic racism is a real part of everyday life, even today, and you can imagine how much worse that was in 1945. So, it is very likely that the difference in terms of risk has mostly to do with social factors and life stressors.

How does early-life education affect the risk of Alzheimer’s?
That is a good question also. You and I are both, of course, in countries where people getting at least an early education is universal, but if you look around the world, that is not the case.

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One of the things that was presented at the conference this year was a new report from The Lancet Commission on Dementia and they have had in their model of life risk for dementia early life education, and this is global.

The way they define this is at least 15 years of formal education and people who have less than 15 years of formal education, which is much more common in lower- and middle-income countries. They found that they are at higher risk of developing dementia than people who are getting 15+ years of formal education.

This probably has to do with cognitive reserve, meaning that you may have people who have more education may have brains that are a little more resilient to the factors that can lead to cognitive decline later, because they may have richer sets of synapses in the brain, for example, or some of the synapses of the brain are working more strongly, for example, than they might if you did not have greater early life education.

That is a little nebulous though. It requires a little bit of speculation because we are just not certain yet exactly what the physiological mechanism is there. We usually put that sort of under the umbrella of cognitive reserve, which I do admit is a bit of a mysterious term, cognitive reserve. What does that mean? Well, the answer is we do not actually know exactly what it means yet. It just needs a bit more research.

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What advice should be given to individuals that suffer from these early risk factors?
I think the number one thing that I would say is that no matter how many risk factors you have, there are things that you can control. However, there are some that cannot be controlled. For example, food quality can be difficult. There are people who just do not have access to high-quality foods or people who do not have access to high-quality healthcare.

But, if there are things that you can do, such as exercise and not isolating yourself. Try to be around other people and make sure that you are saying socially active and socially engaged, and make sure that you are challenging yourself cognitively. Do things that are new to you.

For example, if you normally do not read, but you can and you are literate, you should be reading. If you read a lot, but you are always reading fiction, you may want to challenge yourself to read some non-fiction. If you play puzzles, maybe challenge yourself to also take up a card game. Anything that you can do that is going to challenge yourself mentally in new ways should be beneficial for you as you age.

The other advice I would give is to do more than one thing. We have seen a number of research studies now that suggest that if you control more than one modifiable risk factor, you reduce your risk even further than you would through controlling any one modifiable risk factor alone.

Furthermore, unless you are medically unable to exercise, you should be getting regular exercise that makes you sweat and breathe hard. This kind of exercise is controlling your risk. Again, not everyone has access to very high-quality foods, but most of us can make even just small decisions every day. If you are ready for a late-night snack, reach for the carrots instead of the crisps.

The more positive decisions that you make, the more you are going to reduce your risk for later dementia.

Do you believe that by better identifying these risk factors in individuals, we can reduce the number of people suffering from Alzheimer’s?
I do, but I think it is going to take more than identification. I think it is going to take identification and action, and we can individually take actions on these modifiable risk factors, but we can also take group actions, societal actions, through public health approaches to reduce the overall risk of dementia for everyone as well.

How could this research also provide resources to help have a positive impact on people’s lives?
Some of it is just knowledge. We need to make sure that we are educating the public about these things, which is why we are so grateful for people like you who help get the word out about this research.

We also need to be educating public health officials as well, so it is heartening to me when we see things like the World Health Organization releasing a number of dementia risk reduction guidelines.

The Lancet Commission, which is also a global effort, has released a number of recommendations for public health and government officials.

Where can readers find more information?
https://www.alz.org/aaic/releases_2020/early-life-risk-factors-dementia.asp
https://www.alz.org/alzheimers-dementia/facts-figures
About Dr. Keith Fargo
Keith N. Fargo, Ph.D., is director of Scientific Programs & Outreach at the Alzheimer’s Association. He leads research programs and initiatives to accelerate the Association’s vision of a world without Alzheimer’s and all other dementia.

A key member of the Scientific Engagement team, Dr. Fargo works with all 75 Association chapters, media, and donors to grow understanding of the Association’s role in accelerating Alzheimer’s research and share scientific updates. He is responsible for overseeing the data reported in the Association’s annual Alzheimer’s Disease Facts and Figures, the definitive compilation of national statistics and information conveying the impact of Alzheimer’s and other dementias on individuals, families, government and the nation’s health care system.

Dr. Fargo received his Ph.D. from Indiana University and completed a postdoctoral fellowship at Loyola University Stritch School of Medicine. Before joining the Alzheimer’s Association, Dr. Fargo held positions as a research scientist at the Edward Hines, Jr. VA Hospital Rehabilitation Research & Development Program and an assistant research professor at the Loyola University Chicago Department of Molecular Pharmacology & Therapeutics.