Join Dr. Tania Small, in a compelling 2-part episode featuring Dr. George Grossberg, a world-renowned geriatric psychiatrist who's been at the forefront of Alzheimer’s disease research and innovation for over 40 years. In part 1, they uncover the subtle early signs of Alzheimer’s, the biomarker revolution, and tackle the challenges of health equity in Alzheimer’s care.
Join Dr. Tania Small, in a compelling 2-part episode featuring Dr. George Grossberg, a world-renowned geriatric psychiatrist who's been at the forefront of Alzheimer’s disease research and innovation for over 40 years. With over 400 papers to his name, Dr. Grossberg brings unparalleled insights into the disease.
In part 1, they uncover the subtle early signs of Alzheimer’s, the biomarker revolution, and tackle the challenges of health equity in Alzheimer’s care.
It’s an insightful discussion that prepares you for future trends.
Tania (00:01):
Welcome to Doctors Unscripted. I'm Dr. Tania Small, and I'm here to bring you into a different kind of conversation with some of the brightest minds in medicine and research. It starts with a missed appoint, a wrong turn on a familiar road, and a name you just can't quite remember. But what if memory loss is only the tip of the iceberg? Today, over 7 million Americans are living with Alzheimer's, and that number can nearly double in the next decade. In this episode of Doctors Unscripted, I sit down with world renowned geriatric psychiatrist, Dr. George Grossberg, a trailblazer, an educator, and one of the world's foremost experts in Alzheimer's care for over 40 years. In part one, we've explored the subtle signs, the biomarker revolution, and the inequities shaping who gets diagnosed and when. This isn't just about identifying Alzheimer's disease, it's about recognizing the window to act earlier, smarter, bolder. So, join us as we shatter outdated paradigms because the future of Alzheimer's care is being rewritten. Now, let's get started. Welcome Dr. Grossberg. Thank you.
Dr. Grossberg (01:30):
Tania (01:30):
I'm excited to talk about a topic that affects millions and millions of people and families
Dr. Grossberg (01:36):
Tania (01:36):
To me that's been actually misunderstood, misdiagnosed sometimes, and so happy to have you bring clarity to it.
Dr. Grossberg (01:44):
What topic is that?
Tania (01:45):
And that is Alzheimer's and Alzheimer's psychosis.
Dr. Grossberg (01:48):
I've never heard of that disease. Just kidding. That's kidding. No, that's a very, very important. In fact, it's been just a couple of weeks ago that the US Alzheimer's Association has recalculated the numbers
Speaker 3 (02:01):
And
Dr. Grossberg (02:01):
Now they feel that we have over 7 million Americans that are affected in families with Alzheimer's disease and related disorders. So it's a huge issue. Huge problem.
Tania (02:13):
So before we even go into the details of Alzheimer's, I want the listeners to get to know you on a personal level. So my first question, let's take a step back. What made you decide to go into geriatric psychiatry?
Dr. Grossberg (02:29):
I was doing my residency at a non-for-profit Catholic hospital in St. Louis County, and they ran a clinic in St. Louis County and a very impoverished section of St. Louis County for a free clinic for indigent adults. And the clinic was basically run by the internal medicine residents. And one afternoon I arrived a little before one o'clock and the nurse was head of the clinic Welcome me, hi Dr. Grossberg, and she had all these charts. This is before the era of electronic records, all these charts piled up and she said, oh, a lot of your patients are already here. And they were sitting in little booths where I would go from one to the other. And she said, oh, in booth one we have the lady with congestive heart failure and booth two, we've got the guy with poorly controlled diabetes, and booth three, we have somebody with some other. Every patient became a disease.
Dr. Grossberg (03:27):
And, I had all these patients to see in a limited amount of time. And I said, wow, is this where medicine is moving? I started thinking about assembly line medicine where you have to see so many patients in a limited period of time, and I would never get to know any of them. And I said to myself, as fun as it was to figure out these medical diseases and how to manage them, what I was really interested in addition was what I called the person behind the disease.
(03:56):
And if I have 12 minutes per patient, I'm never going to get to know them. So literally the next day I called over to St. Louis University where I had done my medical training to talk to the residency training director in psychiatry. So I told them I would do better in psychiatry. They interviewed me and they actually accepted me into the residency. But then of course, recognizing that I liked the medical things and I like of course to get to know my patients and their families and the psychiatric things I liked, the brain and neurologic things. That really moved me into geriatric psychiatry, the discipline that brings all of those together in the typical 85-year-old or his family. So that's how it kind of happened.
Tania (04:48):
So Alzheimer's, what I want to do is really even start with the basics. What is Alzheimer's and how is it different than other types of dementia?
Dr. Grossberg (05:03):
So what we know is it is not part of normal aging. It is a specific brain disease. We now think we understand most of the causes, not all, most of the contributors to why cells die in Alzheimer's disease and that it's very, very common and it's different than other brain diseases, other dementias like Lewy body dementia, vascular stroke related, Parkinson's, dementia, frontotemporal, so on and so forth, that it's by far and away the most common cause of not only memory but cognitive loss in later life. And we're learning more and more about how to treat it and how to try to slow it down. It's very exciting and risk factors for it. Then identifying it early.
Tania (05:51):
So if we start with the pathology of Alzheimer's, what do we know now?
Dr. Grossberg (05:56):
So we haven't learned a lot about the pathology. That's different than when Professor Eloise Alzheimer described it in the early 19 hundreds. He described over a hundred years ago, plaques, neurotic or amyloid plaques and neurofibrillary tangles that he saw at autopsy in the first patient that he diagnosed. So the plaques and tangles are still the primary findings that we see in Alzheimer's disease. And the plaque more recently have been a focus for therapy for Alzheimer's disease to try to slow down the deposition of plaque
Speaker 3 (06:38):
And
Dr. Grossberg (06:38):
The evolution of these neurofibrillary tangles, which basically are in the neurons in the cells that cause the cells to kind of become dystrophic or dysfunctional. So those are the key neuropathologic changes, and those have not changed.
Tania (06:55):
What is the clinical manifestations of Alzheimer's in the different stages?
Dr. Grossberg (06:59):
So there are different schemes to staging Alzheimer's disease, but I think what's really important is to try to pick it up early and to diagnose it early and look for the early signs and early symptoms. And they do vary from person to person, but there are some things that are much more common. One of the things that's extremely common early on and what brings people in is that not necessarily the person themselves, the older adults herself or himself, but someone in the family has noticed that mom or dad or grandma grandpa is starting to become more forgetful and not just forgetful, but forgetful to the point where it may be affecting their day-to-day functions. So I'll give you an example of it. So a patient that I saw recently was a woman in her eighties came with her husband and also with a daughter. It's very common, actually came with a couple daughters.
(07:54):
The reason that they came was was that they were concerned because they were getting calls from different stores about their mom leaving her purse in the store. Now, if that had only happened one time, people could say, well, it's possible she forgot her purse. But this was happening almost weekly at different places. And they were calling and saying, Hey, your mom left her purse here and her wallet's in it, and so on and so forth. So that was the earliest kind of manifestation. So there can be problems with short-term memory and recall problems with orientation, problems with higher brain functions like managing a checkbook or being able to drive responsibly. It's a spectrum of cognitive or brain related changes that makes us concerned that something like Alzheimer's disease might be going on.
Tania (08:48):
So at what point is the patient aware that he or she's losing his memory or developing something different? And I ask this because my grandfather was diagnosed with Alzheimer's, again, not officially diagnosed, but clinically, and I remember there was a point where he was embarrassed that he wasn't remembering certain things and was not talking about it. And then he got to a point where he just didn't even know that he didn't know anymore.
Dr. Grossberg (09:16):
Yeah, that's a good point. So it really varies from person to person. Most of the patients that I see are brought by the family.
Speaker 4 (09:25):
They’re not self-referred
Dr. Grossberg (09:27):
So they may not be as aware of the changes that have occurred and the impact of those changes. But the family is very, very much aware. So I had a patient, a very sweet lady in her late eighties was sitting in my office, her husband's next to her and we're doing an initial evaluation, and I'm asking her, by the way, how's your memory been? And she said, oh, my memory's great. In fact, it's probably better than most of my friends who are my age. And the husband who's sitting next to her is shaking his head, no, this is not true. But she wasn't aware. So often the patient doesn't have the insight and the awareness, but sometimes they do. And when they do, it can be very frustrating. It can be particularly difficult because they may not understand exactly what's going on, but they realize that on some level that they're just not able to function as well as they did before. And that can be very disturbing, can be frightening. It's something that's not a positive kind of feeling. State
Tania (10:31):
If you can go a little bit more into the different stages explaining
Dr. Grossberg (10:37):
What
Tania (10:37):
They are, how they manifest.
Dr. Grossberg (10:39):
Yeah, we could talk about the stages. So most people talk about three stages in Alzheimer's disease. I've actually added a fourth stage. So generally speaking, in the early stages, patients are very functional. So their basic activities of daily living are preserved. Things like being able to eat on their own, dressing, bathing, grooming, hygiene, their continent, for example, early stages. Those things are all preserved as you move into language is generally well preserved. As you move into the middle stages, each of those basic areas starts to begin to suffer. So for example, the person may begin to wear the same clothes over and over again if they were able to drive in the very early stages. Now they're getting lost and they're maybe not able to safely drive anymore. Individuals may begin in the middle stages to have a little more difficulty with continence, particularly urinary kind of issues, which can be a problem when they move into the more advanced stages.
(11:42):
One of the hallmarks of that is that they no longer have control of bladder and maybe even bowel functions and language deteriorates. So in the middle stages, families might report that the individual may be searching for words or has difficulty with fluidity of speech. In the more advanced stages, that becomes really a big problem. They may only say a few words here and there. They tend to be much more quiet, much more subdued, lack of spontaneity. So we see different hallmarks. There's a fourth stage, which is what I've called the terminal stage, unfortunately, of Alzheimer's disease. At which point patients often become hospice eligible. They may in fact no longer be able to ambulate. Their balance is not good. They're at risk for falls. They're often in wheelchairs, sometimes even curled in bed, in a fetal position in bed in the nursing home. They may not recognize their loved ones. They're not able to produce any recognizable kind of speech. That's the terminal stage. The broadest stage is that broad middle stage. And our goal with treatments and with lifestyle and so on, even in people that have Alzheimer's disease, is to keep them in that early to middle stage for as long as possible. So what I tell my patients and my families is that we don't yet have a cure for this disease, but our goal is to keep mom as functional as possible for as long as possible.
Tania (13:18):
Yes. When it comes to diagnosing Alzheimer's, at one point, I remember a while ago, they said, well, basically you diagnose it on autopsy if it's true of Alzheimer's. Now I know there's a lot of different diagnostic methodologies that we are using. How are we now diagnosed in Alzheimer's and what is the best method?
Dr. Grossberg (13:42):
Going back a few years, like you pointed out, that's what we used to say was that the only way to be definitive as far as diagnosing Alzheimer's disease is that brain autopsy. And as families would ask us, do you think this is Alzheimer's disease? We'd say, well, the clinical symptoms, they all point to Alzheimer's disease, but we're not sure. The only way that we can be a hundred percent sure is to look at a piece of mom's brain at autopsy, and hopefully
Tania (14:08):
That's what they said to me about my grandfather.
Dr. Grossberg (14:09):
Hopefully that won't happen for many years to come. We want her to live a long life, whatever. So that's what we used to say. But that was before the era of what we call biomarkers.
Speaker 3 (14:19):
Okay.
Dr. Grossberg (14:19):
So in talking about biomarkers, we're looking at a whole range of different things. Probably the earliest biomarker that we had was spinal fluid biomarkers and looking for evidence of the brain disease and the spinal fluid. Now, people in the US are not very eager to have a spinal tap. They don't stand in line to get one. It's not like a blood test. But nonetheless, those that did get spinal taps, we could see evidence of the brain disease in the spinal fluid. So that was probably the earliest biomarker.
Tania (14:52):
Are you looking for what
Dr. Grossberg (14:54):
Amyloid is actually decreased in the spinal fluid, the A beta 42,
Tania (14:58):
And
Dr. Grossberg (14:58):
Then you have increase in the tau, which is part of the neurofibrillary tangles. But looking at that ratio could be very useful in telling us in the spinal fluid, what's going on up in the brain. Right after that, or almost at the same time, neuroimaging biomarkers started to be developed, particularly pet scanning and looking at amyloid pet. There's also tau pet, but amyloid pet where we could visualize the plaque in the brain and we can quantify the amount of plaque in the brain, much more benign, less invasive than a spinal tap, but very, very expensive, very costly, and often not reimbursed by insurance. And many facilities all over the country don't have pet scanners, much less the ability to do amyloid pet rural areas, for example, and so on. But that's another viable biomarker. What people call the holy grail of biomarkers is a blood-based biomarker
Speaker 3 (15:59):
Because
Dr. Grossberg (15:59):
Again, having a simple test, a blood test that's going to have a high level of sensitivity and specificity for Alzheimer's disease is where we are now. We are really in that era, in that time where we have blood tests specific and sensitive blood tests that rival spinal taps and the amyloid PET scan.
Tania (16:22):
And I'm assuming that's the pTau.
Dr. Grossberg (16:25):
pTtau217 is the one that looks most promising and it's relatively affordable, at least compared to a six to $8,000 PET scan and a little bit more tolerable than a spinal tap, just a simple blood test. Hopefully that could be maybe the first round of testing after the clinical scenario indicates that this might be Alzheimer's disease.
Tania (16:48):
When I looked at the data, I think it's about 90% accurate.
Dr. Grossberg (16:52):
That's correct. Maybe a little over 90%. That's exactly right. Exactly. Which is very similar to the other tests that we have. Yeah.
Tania (16:58):
So in the future, do you see just looking at plasma or do you see doing both plasma and pet, where do you see the field going?
Dr. Grossberg (17:05):
Well, because of the expense of the PET scanning, I can see that the blood-based biomarkers may replace the more expensive and not as comfortable to administer testing like spinal fluid testing. So that's the direction that we're moving. The really big question related to what you're asking is will these blood-based biomarkers replace clinical symptomatology
(17:31):
Or the clinical diagnosis? And there's a big argument in the field about whether we should go strictly with the biomarkers or it should be a combination approach. I like the combination approach. I think it's very important to diagnose patients based on clinical symptoms and to get a good detailed history, develop a relationship with the patient and with the family and say, well, we're not sure what the exact diagnosis is, but we need to do some tests. First of all, we need to do some blood work to rule out contributors to memory and cognitive change. Could it be a thyroid problem? Could there be some bad medications on board? We need to review your medicines to make sure there isn't something that can impair memory or cognition. So I think the clinical aspect and differential diagnostic aspect, could the person be depressed and have a so-called dementia syndrome of depression that I think is really, really important. But there's no doubt that blood-based biomarker that's going to become part of the diagnostic process, especially in the areas where you don't have access to the more sophisticated technology. But in general.
Tania (18:44):
So then who should be tested? And I ask this because, so we have patients that show clinical symptoms of Alzheimer's, but then what about those that have a family history of Alzheimer's and yet not show any kind of clinical symptoms?
Dr. Grossberg (18:58):
So that's also a very good question. So we're not sure. So the current thinking is that we want to test people who maybe have clinical symptoms that are suggestive of Alzheimer's disease, and let's say for example, that we do a PET scan, an amyloid PET scan, or we do a blood-based biomarker that's looking also at amyloid and other changes that accompany Alzheimer's disease. If you have a negative amyloid PET scan or you have a negative blood-based biomarker, that's where it's the most useful because it tells you that whatever's going on here, this disease process at this point in time, it's not Alzheimer's disease. If you have a positive biomarker, let's say a blood-based biomarker, it doesn't tell you definitively that that person has clinical Alzheimer's disease. It's not a hundred percent, and it doesn't tell you what stage things are in. Maybe we're in the preclinical stage, but we don't have evidence yet that looking at risk individuals who are totally asymptomatic. But it's a good idea to use any of the biomarkers, whether imaging or spinal fluid or blood-based biomarkers that they're not predictive of who's going to have Alzheimer's disease. But that's a direction that we're moving in.
dTania (20:22):
Going back to the biomarkers, from what I understood, I think an article that came out about a month ago or two where it showed the pizza house pizza
Dr. Grossberg (20:29):
2 1 7, 2 1 7,
Tania (20:30):
They noticed that while it's 90% accurate for the general population, for some reason, I don't know if it was, I think it was in African Americans, it was about 70% accurate.
Dr. Grossberg (20:42):
So you're bringing up another very important point. So most of the norms and the findings that we have are not in the ethnic minority population, so we have to be very, very cautious in how we interpret the data. It may not be as sensitive. You mentioned African-American populations or other kind of ethnic minority populations, whether it's Hispanic populations, Asian populations, and so on. So that data is still emerging. We don't have enough numbers of the minority patients to be as confident as far as the sensitivity and specificity.
Tania (21:18):
And I'm curious to know why would there be a discrepancy? Is it just levels of TAL in the blood?
Dr. Grossberg (21:28):
Yeah, there could be many mean, we'd have to speculate. I mean, I don't know for certain what the reason would be, but again, how people manufacture the plaque or the amyloid plaque and the developmental stages of the plaque may differ in different racial and ethnic groups, the rapidity of synthesis, how it's deposited, to what extent it might be visible on a scan, but that's a tough question to answer. And there can be, of course, genetic loading and genetic vulnerability, which is different in different populations as well.
Tania (22:04):
And I'm also curious, there are maybe different ethnic populations. Are they over-diagnose them with Alzheimer's?
Dr. Grossberg (22:11):
So we know that one of the major risk factors for Alzheimer's disease are things that are bad for the heart, cardiovascular disorders. So in any racial or ethnic group where there may be a higher prevalence, particularly of poorly controlled or not as optimally controlled diabetes or hypertension or heart disease, you're going to see more Alzheimer's disease. And that's true for African-Americans in particular.
Tania (22:38):
So then some recent, I don't even want to call it recent, maybe over the last five years I read that particularly Latinos and African-Americans are diagnosed about two to three years later than their white counterparts as well.
Dr. Grossberg (22:50):
Yeah. So that's another issue. And there are racial disparities. There's no doubt. Part of the reason might be, and I can use kind of our clinic as an example. So we are located in the city of St. Louis, the middle of the city. The city of St. Louis is about 50% African-American. If you look at our memory clinics, our geriatric psychiatry clinics, our neurology clinics and so on, you would think that a 50% or pretty close to that of our patients would be African-American patients. But the reality is it's more like 10%. So often racial minority patients feel more uncomfortable going to the ivory tower,
(23:38):
The big medical center than the usual kind of white patients. They feel more comfortable in their own neighborhood, maybe going to the neighborhood doctor or physician who may not be a specialist. They're a generalist and their suspicion level and their index of suspicion for things like Alzheimer's disease may not be as high as if they come to a specialty clinic. So one of the things that we've been trying to do, and this is especially the case for clinical trials where we're developing new treatments, is to reach out to, in our case, to the African-American community, to go to them rather than expecting them to come to us to set up a memory clinic in North St. Louis, which is one of the centers for the African-American population in collaboration with the primary care doctors, that they have a comfort level going to rather than expecting them to come to us because just not happening.
(24:39):
And this is not just St. Louis, this is all over the country. That's everywhere. It's a big issue. And at least until recently, one of the things that the NIH and the FDA have always emphasized is that we need to recruit more racial and ethnic minority patients into our clinical trials to develop new treatments because they may not respond as well, or they may be more sensitive to side effects to new treatments than the usual population that's included in clinical trials. So it's a big challenge and also an opportunity. It's an opportunity for us to do outreach.
Tania (25:15):
There are a few medications that you see a difference in terms of efficacy, in terms of, to your point, side effects and
Dr. Grossberg (25:23):
Dosing and
Tania (25:24):
Dosing. And I think the diversity action plan that FDA initially required, I think that was huge
Dr. Grossberg (25:31):
And related to what you mentioned before. So the data relative to biomarkers is no different. So the data relative to biomarkers needs more racial and ethnic minority recruits and participants so that we can actually say that this is a blood-based biomarker that's going to be sensitive and specific, not just in white populations, but also in racial and ethnic minority populations.
Tania (25:58):
That's exactly what I was thinking. At least that will widen the net of them being able to pick up patients that potentially have Alzheimer's more than they are doing now.
Dr. Grossberg (26:08):
So we do know that we mentioned African-Americans that they do have a higher rate of Alzheimer's disease, and it may be because of undiagnosed and untreated risk factors, particularly the cardiovascular risk factors. But in all patients, there are just a whole range of different risk factors for Alzheimer's disease that are a modifiable. So we need to do a much better job educating middle-aged individuals that are moving into their later years to basically try to avoid or to manage and treat these risk factors so that we can decrease the rate of Alzheimer's disease later on, or delay the onset of Alzheimer's disease. I mean, all kinds of things. Everything from smoking to obesity to high lipids, cholesterol. I mean, there are many different modifiable risk factors, and the earlier we get them under control, the better one's going to be as far as their risk of Alzheimer's disease. Later.
(27:13):
I was a teenager. I was in high school, and one afternoon I came home. My mother was in the apartment and on the couch of our apartment was this little old lady with gray hair. It was stranger. She thought, come on over. Let me introduce you. This is Mrs. Krazner, and she's going to be living with us. I said, oh, that's interesting. A couple weeks later, this little old lady had multiplied. There were two ladies with gray hair sitting on the couch. Make a long story short, my mom figured out that with her nursing background, she could do a lot better taking care of older people than working on an assembly line for $25 a week. And I grew up with all of these surrogate grandparents. One day, the chair of our department came to the resident group and said, we have a really exciting opportunity. We can go and provide consults in a nursing home. Well, I'll tell you, every resident in that room except for me, moved to the back of the room. They didn't have anything to do with these old people in nursing homes. Whereas I stayed in front and I said, Hey, that's great. I'll go. I had this comfort level and I just felt good about it. That's something that was threatening to me.