Alzheimer’s Disease: Medical Advances and the Importance of a Compassionate Approach

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Every minute, a person in the United States is diagnosed with Alzheimer’s disease, a brain disease that slowly destroys memory and other mental functions. While some risk factors, such as a head injury or genes, may not be completely avoidable, other, more controllable factors may impact whether you develop Alzheimer’s. Alan Lerner, MD, Director of the Brain Health and Memory Center at University Hospitals, shares promising research in this area and gives a humanistic perspective on a disease that’s been called The Long Goodbye.

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Macie Jepson
A big part of Healthy@UH is (that) we break down medical myths with scientific facts has been the result of Pete and I, and our Healthy@UH team leaning on our personal experiences. I always knew that this time would come, and that would be the right time to talk about my most profound personal experience medically, which was slowly watching my mom slip away. She eventually didn’t know me. It was a nine-year goodbye that began when she was only 65 years old, struggling to find her words, and eventually, she tried to find her parents who had passed years ago; then eventually, she didn’t know that she had a husband and that she had children, and she didn’t even know how to feed herself. So yes, I’m talking about Alzheimer’s, Pete. Yeah. We were emotionally pulled into every single headline about early diagnosis, about treatments and, of course, about cures, but my mom died the week before Christmas four years ago, and I really do still hold out hope even through that experience, Pete, because I hope that science will prevail, and one day we’re going to see an end to the suffering for other families and perhaps even mine.

Pete Kenworthy
Yeah. I’m sure that was extremely difficult for you, for your husband, for your girls, and here’s a number that’s hard to believe, Macie: just about every minute, someone in America is diagnosed with Alzheimer’s. Every minute. Here’s the other one that got me. Many cases of Alzheimer’s are preventable. Hi everyone, I’m Pete Kenworthy.

Macie Jepson
… and I’m Macie Jepson, and this is Healthy@UH. Today we are talking about Alzheimer’s. Brain health. We’re talking about dementia. Is there anything we can do to prevent these, and is there anything we can do to treat them? Joining us today as Dr. Alan Lerner, Director of the Brain Health and Memory Center at University Hospitals, Cleveland Medical Center. Dr. Lerner, thank you for joining us today.

Dr. Alan Lerner
Good morning.

Macie Jepson
Let’s start broadly. How does Alzheimer’s impact the body and how is it different from dementia?

Dr. Alan Lerner
Dementia is defined as memory loss, accompanied by functional loss. So, there’s memory loss, like I can’t remember when my appointment is, but I’ll get the answer. Functional impairment tends to start with the most complicated things we do, and that’s financing and driving, and those are things that we don’t let children do. So, by the time – and even in your story – it was a long time before she didn’t recognize her husband or you. That was really at the end of a very long journey. So, it’s not, those sort of basic things are things that come the last. Dementia itself is a symptom, like pain, fever, cough. If I have a cough, it might be COVID, might be postnasal drip, could be lung cancer or tuberculosis or many other causes. Similarly, dementia has many different causes, and part of the assessment process is to look at what are those many causes. We estimate that about at 60% of cases of people with severe memory loss are Alzheimer’s disease. We also know that in older populations, those people let’s say over age 80, mixed dementia; Alzheimer’s plus something else, a stroke, scars in the brain, other causes coexist. So, we should think about the concept of mixed dementia, particularly in older populations.

Macie Jepson
Before we move on, what is it that Alzheimer’s does to the body?

Dr. Alan Lerner
Alzheimer’s is primarily a brain disease, and it is not found in other organs in the body. It is characterized by the deposition of two proteins in the brain. One is called amyloid, and one is called tau. The current thinking is that these start depositing in the brain possibly as much as 20 years prior to any symptoms. The brain has a tremendous amount of resilience and safety margin built in. The idea is that if somebody starts showing memory loss at age 75, it’s possible that some of the changes in the brain have been there for as much as 20 years, and this is also part of the rationale for treating people early, as we’ll talk about soon.

Macie Jepson
When you say changes in the brain, are we talking plaque buildup in the brain or is that oversimplifying?

Dr. Alan Lerner
The plaque is what’s called amyloid, and that deposits outside of the nerve cells, and inside of the nerve cells are deposits of tau protein, so-called neurofibrillary tangles. Another thing I should mention about amyloid is the removal of amyloid from the brain by medications. In 2021, the Food and Drug Administration approved a new drug for Alzheimer’s disease, the first in over 15 years. This is a drug known as aducanumab or Aduhelm, and is manufactured by Biogen, a large pharmaceutical company. This has been controversial for a number of reasons. One thing is clear, that it does remove amyloid from the brain that might have been there for many years. A lot of people and specifically those people who are experts in Alzheimer’s disease have come out against the use of Aduhelm. Prominent institutions, University Hospitals included, the Cleveland Clinic Foundation, Mount Sinai Hospital in New York have elected not to use this on any widespread basis.

There are a number of reasons why this has happened, and the company has changed some of the packaging even within the first month, and they’ve recently cut the cost because it was not felt to be efficacious over the long run, which has been primarily studied in about a one and a half year study. Almost all of the people at that end of that one and a half year study were worse. The people who took the drug compared to those who took the lookalike placebo was slightly better, but many people do not feel that that was significantly improvement to spend $100,000 per year, possibly as much of as that. The other thing is there is some side effects that would seem to affect as many as 40% of people who take this, including brain swelling and brain hemorrhage.

However, we should think that this is an important message, that there is hope that other pharmaceuticals that could deliver similar results with less side effects, possibly with less cost, may be in the offing and is a lively area of research, including research that we’ve done for many years here at University Hospitals trying to prevent Alzheimer’s Disease. So, looking unlike the Aduhelm studies, which looked at people who are already affected, we have been doing studies for many years in people at high risk who have amyloid in their brain, but are clinically normal and to see whether the removal of amyloid at earlier stages of the disease, in the pre-symptomatic phase, might be of some value, and these are ongoing studies.

Pete Kenworthy
So, many people are diagnosed each year. More than 5 million Americans have Alzheimer’s, so, before we talk about the fact that millions of cases may be preventable, what is the current treatment plan for someone who is diagnosed with Alzheimer’s, and does it help? We know it’s not curable right now, but does detecting it early matter?

Dr. Alan Lerner
The current treatment plan beyond assessment and is it dementia or is it something that’s treatable such as depression or hydrocephalus or traumatic brain injury that could be preventable or stroke that could be preventable from getting worse? The treatment relies primarily on two types of medications. One are medications that block the breakdown of a chemical in the brain called acetylcholine, which is important for memory, and these are medications like Aricept, Exelon and galantamine, and the other is a medication called memantine, also known as Namenda, that seems to block the injury of cells.

Pete Kenworthy
Then early detection, does that make a difference as far as treatment goes for the patient?

Dr. Alan Lerner
The issue here goes beyond medication and into things such as life planning. In other words, can they remain in their home? Who’s providing their meals? Are they being well taken care of? Many people now with Alzheimer’s disease or the early stages of it, which is known as mild cognitive impairment, are living independently, and so it’s, that’s part of it. Now, in every other disease that we know, early intervention works, and this is a big thing going forward. Can we intervene significantly and make a difference over the long term? We don’t wait until you’re in the ICU with a fever to treat your urinary tract infection. We don’t wait until you’re gurgling up pink fluid to treat your congestive heart failure. We don’t wait until that abscess results in, you know, sepsis and shock to treat. So, in cancer, if it was the pea size cancer, we don’t wait till it’s the lemon size cancer. You’d run the other way…and so the idea of early intervention is very alluring. It still remains to be proven. And this is not just true in Alzheimer’s disease. It’s true in other conditions whether early intervention will work, but in general, we think that early intervention is the way to go.

Macie Jepson
Well, you mentioned a couple of those medications, and there are only a couple of types that are on the market, and I guess common sense, in my mind, my uneducated mind, would think that the earlier you get to take that, then the better off you are, especially if this stuff is happening in your brain for years prior to knowing.

Dr. Alan Lerner
People have looked at this issue, and actually, although it’s somewhat counterintuitive, dementia is really the last thing that happens. We talked about amyloid and tau depositing in the brain at the pre-symptomatic phase. So, when somebody is symptomatic, dementia’s actually the last thing that happens, and these medications don’t actually help at these earlier stages. Even in mild cognitive impairment, they don’t help that much. One thing that may help that I have not mentioned is vitamin E. And we have a actually studied vitamin E several times, and doses of vitamin E may slow down the progression of memory loss.

Macie Jepson
Oh, interesting to know. Well, obviously this isn’t getting any better. By 2025, studies show it’s expected that cases in America will top 7 million. So, Doctor, what do we know about what causes this? Because knowing that you would think we’d be able to, to stop it somehow.

Dr. Alan Lerner
A lot of focus has been on age as a risk factor. We know that people with Down Syndrome, who have an extra copy of chromosome 21, where the amyloid protein is, develop it usually at an earlier age, and also that there are genetic markers. For early onset Alzheimer’s disease, there are several rare genes that cause it. There is a gene called APOE or APO lipoprotein E, which comes in three types: E2, E3 and E4. And having one or more copies of the E4 gene do predispose to late onset Alzheimer’s disease. We also think that lifestyle may have a important function here: nutrition, diet, exercise.

Macie Jepson
It always goes back to that, doesn’t it? (laughs)

Dr. Alan Lerner
The so-called mom and apple pie things. Everybody should be doing this, and it’s about not just about brain health, it’s about health.

Pete Kenworthy
Can we really change what we eat to prevent Alzheimer’s? And I’m asking that because I read the rate of the disease is highest in people who consume Western diets, right? An emphasis on meats. In fact, there was a study that showed Africans, Japanese and Chinese living in the U S have a higher Alzheimer’s risk than those same people living in their home countries.

Dr. Alan Lerner
These are very important questions, and obviously, diet and exercise are things that have to be measured in decades and not in years, and the same is true of brain games, the idea that you may slow the process down. It’s not a one time thing, and it takes years to show results from these things. So, diet is important. The whole mantra here is what’s good for the heart is good for the brain, and we know the effects of hypertension and diabetes on the brain are also quite profound, and diabetics are at higher risk of developing Alzheimer’s disease. People with hypertension are also at higher risk.

Pete Kenworthy
So, that all makes sense in terms of lifestyle, right? Taking care of your body, looking out for what’s good for your heart will also take care of your brain, but what about this idea…cause this is out there…this idea of reversing Alzheimer’s with your diet, right? There are books out there that say depending on what you eat, you can reverse, once you have the symptoms, you can go back in the other direction. Or supplements or things you can take to go back in the other direction. What about that? Is that a bunch of hooey or is that actually possible?

Dr. Alan Lerner
I think there’s certainly hope there, but I don’t think that we’ve found anybody who had Alzheimer’s disease who no longer has Alzheimer’s disease. That would be a cure, and if we knew about that, we wouldn’t be talking about it. We’d be acting on it. Supplements, some of them have been looked at rigorously and some of them have not, and that’s an important thing, and I think supplements need to be treated as if they were medications. Do they work? What dose? This is especially a problem with natural products. For many years, people took Ginkgo, and it was eventually studied and didn’t show very much, but there’s the whole issue about what part of Ginkgo and, you know, it’s similar with cannabis, you know. CBD or THC 9 or THC 8? You know, there’s hundreds of compounds in the plant. You know, which ones? Which dose? Which formulation? How often? These are important questions to which we don’t necessarily have the answer. A lot of the issue with lifestyle change is that it should be intuitively obvious to exercise, to have a healthy diet, to avoid trauma, to not smoke, to keep your diabetes and hypertension under control. They do have an effect. It’s certainly a marginal effect, but I don’t think that we have seen any cures to date.

Macie Jepson
Doctor, why are almost two thirds of American cases women?

Dr. Alan Lerner
Women certainly live longer, and age is one of the highest risk factors. People have looked at things such as estrogens, whether they were protective or not. It’s unclear about that. In the case of APOE gene, women have a higher risk with the same genetic makeup as men.

Pete Kenworthy
Okay, you mentioned trauma. Let’s talk about traumatic brain injury for a minute. Macie, your mom suffered from a TBI.

Macie Jepson
She did, and I’ve often wondered if that had anything to do with it. So, she fell. She hit her head. She was in a coma, and because of that, she actually had seizures throughout her life, so, yeah, I’d love to know more about that.

Pete Kenworthy
And she did that early in her life, right? But I wonder about younger people maybe who were near explosions, right? Or had concussions, right? Is there a direct connection here?

Dr. Alan Lerner
Overall, there is a connection between a history of a head injury and the development of dementia due to Alzheimer’s disease. Head injury itself is very heterogeneous. The falls or then versus repetitive head injury. This has come to light because of football players and with the repetitive sub-concussive blows. We all love the highlight reel, but think about what the effect of that is, and certainly, head injury can occur in any sport. Swimmers who hit the wall, lacrosse players, hockey players, baseball players who get hit in the head as well. The form of dementia that’s found there is what’s called Chronic Traumatic Encephalopathy or CTE, and it’s been found in more than just football players. Now, there’s no obligate need to play football, certainly at the professional level, and again, trauma does have a dose effect. So, in other words, the more hits the worse the problems.

There are some similarities in the idea that the protein called tau deposits in Chronic Traumatic Encephalopathy. And this is almost another one of these Holy Grails. Is there an environmental cause of Alzheimer’s disease? People have looked at this in identical twins. So, there are identical twins who are genetically identical, but are discordant for things like Alzheimer’s disease. So, this is a fertile area for looking at. Are there environmental differences, dietary differences? People have also looked at other sort of interesting models: the religious orders, nuns and priests who, although not genetically related, spend decades in similar environments, and to see whether they have differences that could show up on the basis of that. There’s been a very big ongoing study of a large family near Medellin, Colombia who have a genetic cause of Alzheimer’s disease in what’s called Presenilin-1 mutation, which is probably one of the more common of a very rare variant.

So people have looked at that, and this is an ongoing study of people getting Alzheimer’s disease, even as early as their 30s or 40s, and in fact, there was a recent report of somebody who seemed to be resilient, and although they had the genetic component that should have predicted Alzheimer’s disease, they had a genetic, another genetic difference that seemed to protect them to a great extent. So, this is an ongoing thing in this large family, somewhat similar to what happened in Huntington’s disease, where there was a large family in Venezuela that was studied and led to the identification of the Huntington’s disease gene.

Pete Kenworthy
Earlier, you touched briefly on some research that was being done at UH. Before we let you go, where are we in terms of research? And not just at UH, I’m curious, you know, worldwide, what gives us hope for the future and how soon will that be here?

Dr. Alan Lerner
One of the things that gives us hope is that the National Institutes of Health is spending almost $3 billion a year, which is up almost 100% over a few years ago, so, to bring new people into the field to make new discoveries, both at the basic level, as well as in clinical research studies is important and ongoing, and I think that this is really a great thing. There is some evidence that in Western countries – Germany, France, England, the United States – that dementia rates are actually on the decline already, even as the dementia prevalence goes up because of the aging of the population that the dementia incidents rates seem to be going down, and some of this may be due to lifestyle changes that we’ve heard so much about in other contexts: heart disease, diabetes, education, diet, nutrition, exercise. So, one of the other issues that always comes up is the whole issue of social engagement, both as a treatment, as well as a preventative.

Now, we have to recognize that COVID has done a huge number on this because this is one of the bedrocks of maintaining familiar social relationships. As Macie pointed out, that was one of the core things that she talked about was how did her mother relate to others? Well, COVID has changed that in profound ways, and a lot of people are very concerned, and there is some evidence emerging that people with dementia, A) get COVID more; they’re older and B) do worse once they get that.

I’ve been in this field for almost 30 years, and we’ve made amazing advances in imaging and in diagnostic techniques. One of the things that’s also been held out is the Alzheimer’s blood test, and we really are making tremendous progress with this looking at early intervention. Can we predict who has amyloid in their brain? Because the ways that we can really get to that definitively are either expensive, such as a Positron Emission Tomography, or PET scan or invasive, spinal taps, and the idea of the Alzheimer’s blood test that can be widely used and pick out people at high risk for early intervention is very important, and we are beginning to see the commercialization and licensing and availability of these blood tests, and I think this is a growth area in terms of how we’re going to be able to look at this across the University Hospitals system. There’s thousands and thousands of people possibly who could be available for studies of early intervention, which is what I got asked earlier, and how do we identify those people? How do we get them to do the lifestyle changes that might be necessary as well as participate in clinical research that holds the hope for better treatments and cures?

There was a study a number of years ago, and this was also done at University Hospitals, amongst other centers, which gave people their genetic risk information. This was at a time when there was nothing else to be done for them. The only thing they did differently was buy more long-term care life insurance. So, it’s about life planning, and everybody should be involved in life planning. You don’t wait for retirement to plan for retirement. You know, dementia and Alzheimer’s disease is a possibility, not for most people, it’s not a specific probability that they’re 100% likely to get it with some exceptions. So, they need to be able to do things like life planning. There have been some other interesting discoveries, and all of them are important and need to be put into perspective, and this is the finding of a form of tau protein in the blood called acetylated tau that seems to be related to head injuries or repetitive head injuries. So, this is another way of looking at new diagnostics that are coming out, and presumably if we could alter that through some other means that it could be a pharmaceutical type intervention.

Pete Kenworthy
You’re talking about altering the impact on the tau. Is that what you’re saying?

Dr. Alan Lerner
Yes. So, this is the work of Andrew Pieper here at the Harrington Discovery Institute at University Hospitals.

Macie Jepson
Doctor, before we wrap up, is there anything else that you want to mention? Anything we didn’t touch on?

Dr. Alan Lerner
Yes. I think we need to talk about the humanistic aspects of Alzheimer’s disease. Fundamentally, Alzheimer’s disease is about people. It’s not about scans. It’s not about amyloid, tau, zillion dollar machines, epidemiological studies. It’s about people, and I think that this is really important to recognize that there’s somebody there who may be lonely, scared, worrying about the changes that are occurring. I mean, that’s certainly true in their families, but we should recognize that Alzheimer’s disease is about people, and that that really needs to be the focus as we go through this.

Macie Jepson
It’s a nice way to end it, and you are right.

Dr. Alan Lerner
Yes. Thank you.

Macie Jepson
I wish I’d had more conversations with my mom about those things, rather than constantly talking about a cure and what we can do for her next and what test and…

Dr. Alan Lerner
Well, you know, people say, you know, what more can I do for my loved one with Alzheimer’s disease? I think sometimes we don’t always recognize how much we are doing. We’re helping them. We’re taking care of them. We’re spending time with them. We’re driving them places and taking over their finances, and what more can we really expect? This is an enormous thing of the caregiving aspects of 5 million people involves probably 50 million people, and it has touched almost every family and everybody that has a family member or knows somebody who has a family member, and so it’s really a societal problem, but it’s also an individual problem. We really need to not lose sight of the fact that there’s really a person involved in this, and that’s been a key in my clinical practice here at University Hospitals.

Macie Jepson
Thank you for reminding us of that, Dr. Lerner, Director of the Brain Health and Memory Center at University Hospitals, Cleveland Medical Center, and we thank you for joining us today.

Dr. Alan Lerner
You’re quite welcome.