Spotlight on Care: Alzheimer's Caregiving

Alzheimer's Disease and the Rise in Pseudomedicine with Dr. Joshua Grill

March 09, 2023 UCI MIND Season 1 Episode 31
Spotlight on Care: Alzheimer's Caregiving
Alzheimer's Disease and the Rise in Pseudomedicine with Dr. Joshua Grill
Show Notes Transcript

Dr. Joshua Grill, PhD, is a professor at UC Irvine in the departments of Psychiatry & Human Behavior and Neurobiology and Behavior, as well as the director of UCI MIND. Dr. Grill joins Steve to discuss risk factors for Alzheimer’s disease, steps people can take to lower their risk and the promising investigational therapies. He also cautions listeners about the prevalence of pseudomedicine for dementia.

Intro 00:06

From the University of California, Irvine, this is UCI MIND, spotlight on care, the podcast where we share stories, experiences, tips and advice on caring for loved ones affected by Alzheimer's and other dementias. 


Steve 00:22

Welcome everyone to a new episode of spotlight on care. Unfortunately, Virginia is not going to be with me today. But we are excited to have with us kind of our mentor as it comes to Alzheimer's disease. Dr. Josh Grill is going to be with us. And he's going to be talking about pseudo medicine, and talking about what you should do about your brain health. And what you should be wary of. There's a lot of information out there, and I know Josh is going to touch on as much of it as we can. So let me introduce Josh, Joshua D Grill. His PhD, he's the Associate Professor in the department's of psychiatry and human behavior and neurology and behavior at the University of California, Irvine. More importantly, in my mind, he's the director of the Institute of memory impairments and neurological disorders called UCI mind. And he's also the director of UCIs Alzheimer's Disease Research Center. These are two of the most important things going on at UCI, in my opinion, having to do with the looking for cures and looking for ways to advance research on Alzheimer's. So welcome, Josh. 


Josh 01:28

Thank you very much, Steve. 


Steve 01:29

Let's start off with can we predict who will get Alzheimer's and dementia?


Josh 01:35

Sure, well, let me begin by saying what a great job you've done with this podcast you and Virginia. And I'm really honored to be a guest finally, on this podcast, because I think it's become such an incredible resource for families. And I think being a resource for families and for caregivers is a big part of the mission of UCI mind and the ADRC. And I think that this topic that we're going to talk about today is a really key and important aspect that speaks to that mission, that we really need to be a source for trusted information about where we're at as a field, what the evidence really tells us, and in some cases where the evidence isn't quite there yet. So you know, a lot of people ask us, can you tell if I'll someday get Alzheimer's disease, and many, many surveys have been done that tell us that a majority of people want to know whether they're going to someday get Alzheimer's disease and, and when that test comes out that that blood test or that brain scan that can definitively predict who will and who won't get Alzheimer's disease, people will be lined up at the door wanting to take it. But we don't have that test yet. I think there's a lot of really promising research, we're incorporating that research about trying to predict who's most at risk into studies, even studies of promising interventions. But it's still the case that today in 2022, I can't bring someone in who's cognitively normal, who doesn't have memory problems or other thinking problems and run a series of tests and definitively determine whether they will or will not someday succumb to Alzheimer's disease. What we can do is, share with people what we're learning about the risk factors for these diseases, help people understand their own risk, and help them understand the tests that are out there and what they can and cannot tell people about that risk. 


Steve 03:42

And that's great. Let's move on to talking about then what is the greatest Risk risk for dementia?


Josh 03:48

Well, so it's important to remember that the single strongest risk factor for dementia is increasing age. That's the one risk factor we really can't do anything about. We can't slow the aging process. Try as we may. That's the most powerful risk factor.


Steve 04:02

Would you mind commenting about the doubling effect? I'm not sure that we've covered that in one of our podcasts. 


Josh 04:09

Sure. We often say that after age 65, the risk of getting Alzheimer's disease doubles for every five years of life. This is this is part of the equation, but it's certainly not the whole equation. And what that really means is that, you know if a relatively small proportion of people have Alzheimer's disease at age 65, that that proportion would double by 70 and double again by 75. You know, there are a lot of numbers that get thrown around by 80 or 85. The overall risk for Alzheimer's disease may be as high as 40%. But I think it's really important to remember that thankfully, this is not a disease everyone gets if they live long enough. And so understanding the other risk factors aside from age is really so critical. and such an intense area of study. And I generally divide those risk factors into two big buckets. Genes matter, family history and genes matter. So the genes we carry, we get a copy from mom and a copy from dad and the field has discovered many, many genes now that have a role in the risk for Alzheimer's disease. Adding all of those genes together, however, still doesn't tell us who will and will not get Alzheimer's disease.


Steve 05:33

How many genes is it?


Josh 05:34

 Well, over 40 genes have been identified. Most of them are not of major risk changing impact. Most of them have small effects, and may actually be quite common. But don't give us a whole lot of information. And again, even taking all of the genetic information. And there's a lot of impressive studies doing things like poly genomic scoring, we still can't tell who will and won't get Alzheimer's disease. Now there is one gene that is of greater contribution to relative risk than others. And we call that the APOE gene. It stands for Apolipoprotein E And it's been in the news a lot lately, and we've written about it on the UCI mind blog, because this gene does have more impact on risk than the others. And it's available through direct to consumer testing, people can learn their APOE genotype through some of those companies that are out there that offer this. I'm not paternalistic about these things. I understand why people want to know their risk, including learning their APOE genotype. But I do like to caution people that before you learn your APOE genotype, you should talk to a professional you should talk to a geneticist or a genetic counselor or even a researcher if one feels comfortable talking about these issues. But genetic counselors are certainly the best people to talk to before taking any genetic tests, including the APOE gene test. And again, the things that the genetic counselor will tell you is that you know, you can have this test it doesn't tell you if you will or won't get Alzheimer's disease. 


Steve 07:24

Yeah, Dr. Hohsfield, talked a great deal about the and warned us or, warned our audience about genetic testing and making sure that you're getting great advice about it. So. So the other version, besides genes is


Josh 07:40

Yeah, so if if genes make up about half of the risk for Alzheimer's disease, and that's what most of the geneticists estimate the total risk to be attributable to genes. The other half is environment and lifestyle. And this is increasingly clear that how we live our lives, how we treat our bodies, and how we treat our brains throughout life impacts our our risk for getting cognitive problems later in life, including Alzheimer's disease. And this includes, you know, some of the easy recommendations that we can make. So if you have high blood pressure, you want to work with your doctor to control your blood pressure. If you have high cholesterol, you want to work with your doctor to control your cholesterol. Of course great ways to do both of those things is through diet and exercise. And both of those things seem to not only lower these other risk factors like blood pressure and cholesterol, but seem to have benefit on their own. So you don't have to have high blood pressure, high cholesterol to benefit from diet and exercise. And there are many, many studies underway testing whether things like diet or exercise can actually lower risk for Alzheimer's disease. There's still a lot of work that needs to be done. You know, what's the right dose of exercise? How often do we need it? Do you have to run a triathlon to get the benefits of exercise? Most certainly you do not. But how much exercise do we need to benefit our brain the most? That's an open question. On the diet side, you know, avoiding foods that are high in fat and cholesterol is very good for us, but making sure we get enough foods that are brain healthy. This would include the healthy fats we get from fish oils best by eating fish, or things like olive oil and nuts have a lot of these healthy fats, dark green leafy vegetables and the and the fruits and berries that are high in antioxidants. All of these things do seem to be to be very beneficial. We should strive to stay mentally and cognitively active just as we should strive to stay physically active as we age. These things do seem to matter. And the other one that I really try to recommend regularly is making sure we're getting a good amount of sleep, not getting enough sleep or having sleep conditions like like apnea does appear to increase our risk for having a brain problems later in life. And so if you're a person that may not be getting enough sleep or the quality of the sleep that you're getting, isn't that good. Meaning that when you, when you wake up in the morning, you don't feel rested, or you're having trouble staying awake during the day, things like that, then you really want to talk to your doctor about your sleep, and even consider asking for a referral to a sleep physician, and undergoing things like sleep testing to make sure that your sleep is optimized, because it is pretty clear that sleep is critical to brain health. And there are numerous links between sleep and Alzheimer's disease that have been demonstrated. Now. Again, it's not definitive, it's not as simple as if you don't get enough sleep, you'll get Alzheimer's or vice versa. But getting a good night's sleep does seem really key. And I think it's important to say that a lot of this has been sort of codified now. The there's a something called the Lancet Commission that has been really lauded in our field been a rallying cry for a lot of studies.


Steve 11:17

Are you now talking about ways that that some of these lifestyle changes have been have proven proven and or at least in indications are that we're on the right track?


Josh 11:26

Yeah, what I'm talking about is the fact that multiple groups have now taken the information on lifestyle risk factors and felt we've achieved a place where we can make these recommendations as a list of things that people should be trying to do. And I mentioned the Lancet Commission. This is a famous medical journal out of out of the UK, the Lancet Commission has been a rallying cry, we're seeing a lot of clinical trials to test these things. But organizations like the AARP and the global global Council on brain health, the Alzheimer's Association, the World Health Organization, and the American Heart Association have all made recommendations about brain health with age, and they're all relatively similar. And they all include the things that I just mentioned, and a handful of other things. And so, you know, I think there is growing consensus that these things can be can be strongly recommended to people to try to improve their brain health and lower their risk for dementia. And there is growing evidence that these things matter. Namely, there are numerous studies from the United States, the United Kingdom, some Scandinavian countries that suggest, while the overall number of people living with dementia is growing, as our aging population continues to grow, that the incidence of dementia is ever so slightly on the decline. So the number of people per number of people at a given age has, who get who get dementia has come down by 1% per decade, for the last few decades. And that, that matters to public health. And most of us attribute it to greater opportunities for higher education and complex careers. Understanding about these other risk factors understanding the value of, of physical exercise and healthy diets. Again, you know, the fastest growing segment of our population is the people who are at risk for Alzheimer's disease. So we do expect that the global prevalence of the disease is going to continue to rise. But these trends and public health data suggests that these things can and do matter. All that said, there's still no recipe for 100% prevention, there's still no way that I can say to someone if you do X, Y, and Z, or even a list of 12 or 15 things that can certainly guarantee you'll never get Alzheimer's or dementia. That's just not possible.


Steve 14:04

So you've been recommending that I eat salmon five days a week. I know we're kidding here. But that's not going to necessarily be a guarantee.



Josh 14:13

There are no guarantees, and anyone offering them is really not being honest.


Steve 14:19

Well, let's go and talk about that for a second. So there's been this term pseudo medicine, I don't know whether you invented it or someone else invented it. But this is a growing topic about all of these so called Brain drugs that you can take, or supplements, particularly that you can take that are preventative and curative to some degree in terms of the claims. So what what's what's causing this rise in in these types of supplements and interventions?


Josh 14:53

So let me first say I can't take credit for the term and I really first came across the term myself from A couple of really outstanding articles from friends and colleagues at UCSF writing about pseudo medicine for dementia. My colleagues, Gil Rabinovich, Bruce Miller and Joanna Hellmuth really led the way in this, and I agree with them 100% That this is incredibly important and something that ADRCs and experts in the field need to pay more attention to and do a better job of talking about so that people really are armed with information. Why is this happening? You know, Alzheimer's disease, depending on the survey is the most feared disease or the second most feared disease. I think this is going to change soon. But there's still no disease modifying therapy for Alzheimer's disease that's widely available. We don't have enough to offer families who are dealing with this disease who have family members living with dementia, we don't have enough to offer people who are concerned about getting this disease themselves. And it's and it's feared, and there's desperation. And there are people willing to take advantage of that desperation for their own financial gain. So what is pseudo medicine? It's people who will capitalize on on the desperation, many of us feel, I certainly feel a desperation to see the field make advances toward evidence based therapies that can can have better benefits for families can actually lower risk or delay the onset of these diseases. And I am so optimistic and excited about where we're at as a field. But there's still a lot of work to do. And there's there's really no such options as yet. And so, you know, I think we need to be clear about what we can and can't offer what can and can't be promised and educate people about what to look for. And you know, how to distinguish things that are evidence based from things that may be groups willing to take advantage of your desperation for their own financial gain?


Steve 17:05

Well, let's talk about some of those. Not necessarily specific companies, but the categories. There's a lot of television commercials out there with products that are promoting brain health, and the fact that you can almost cure or delay the activity in terms of what's going on in terms of cognitive problems.  And well, how do these companies get out there and promote themselves with that? And do they have the research?


Josh 17:34

Right? So the supplement industry has ballooned into something like a $90 billion industry? So so there's a lot of financial reason that these companies are doing this. And again, Alzheimer's disease is a feared condition. It's a it's a very prevalent condition, and it's a huge market. There have been studies of supplements, laboratory studies that, you know, some of these companies will point to as evidence to support the use of their products, or have even been prevention trials. Very large, very expensive, very important prevention trials that fairly definitively told us, for example, gingko biloba does not prevent Alzheimer's disease does not prevent memory decline, also studies of things like Selenium and vitamin E, again, evidence against the notion that these things can be used to prevent Alzheimer's disease. So what should people be on the lookout for? Well, one, I'm going to read a statement that accompanies a lot of products. Quote, unquote, these statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This is an admission by companies that they are not doing drug development, as we think about it in this country. They are avoiding FDA review for these products. And for the indications that you might be hearing about in these TV commercials or other paid advertisements. You'll see things like infomercials, you'll see things like paid actors who may be wearing a white coat or talking about how these treatments made their memory so much better. There are many levels of frankly, what I call trickery. The some of these companies will go to to market their product, and they'll point to legitimate research, sometimes mouse studies or cells in the dish. But again, they won't have the rigorous clinical trials to support, the use of the product to improve memory performance, let alone to lower risk for Alzheimer's disease or slow its course. Some of them will claim to have clinical trial data. But again, you know, the clinical trial data has never been submitted to the FDA. And oftentimes, it hasn't even been submitted for rigorous peer review at a journal. And, you know, if it were submitted for peer review, there are a number of issues that might be brought up about the evidence that some of these companies present for example, even if they're doing a controlled study, which oftentimes they aren't, they're often doing what we call open label studies where everybody gets the drug and placebo effect, I assure you is a very real thing. And so you don't have an opportunity to compare against the placebo in in these open label clinical trials, in the trials that may have a placebo group or control group, whether it's a true placebo versus historical control, is a question. And again, even in the ones that have adequate placebo controls, we'll see things like many, many, many outcomes that are used to assess potential efficacy and then cherry picking the ones that suggest a benefit, and not reporting or ignoring the ones that don't show a benefit. So given the opportunity to perform rigorous reviews of these things, they rarely, if ever stand up to the test of of scientific peer review,


Steve 21:32

let's bring it back to the person at home who's sitting worrying about their loved one and saying to themselves, well, I just heard or I just saw this commercial or I just had this piece of advice about whatever beeswax or whatever it might be that I should be eating or my loved one should be eating to take care of this issue, what do they do?


Josh 21:54

So first and foremost is you or your family needs to talk to your doctor. Now, I do want to say there are some legitimate uses of supplements if you're allergic to something and that causes deficiencies. Or if you have other deficiencies that show up in laboratory tests, your may doctor may talk to you about supplementing your diet in order to treat what they're finding in those laboratory reports. It's really the issue when you're not deficient in something where there's really very little evidence to support dietary supplements and, and almost no evidence in the space of age related cognitive changes or Alzheimer's disease. So first and foremost, you want to talk to your doctor, I want to I think it's really important to say some of these things can also be dangerous. You know, take taking it too high of dose, for example, Vitamin E has been shown to be associated with negative cardiovascular outcomes. And again, in part because there are a dearth of lack of rigorous clinical trials of a lot of these things. We have very limited information about how these things may interact with each other multiple supplements, or how supplements or other products could interact with prescription medications. And you know, I think that all the more reason to talk to your doctor before beginning any new vitamin or supplement or other, you know, treatment for memory problems that that you learn about through other channels besides your doctor, because you really want to make sure that you're not doing harm with these things.


Steve 23:35

I've heard you say that when it comes to like Omega supplements and things like that, that the reality is, is that the real food is far better for you than than the supplements unless the doctor says you're not getting enough.


Josh 23:49

Again, I think you want to talk to a doctor before you do any of these things. My opinion is that a common path for these things is that epidemiologic studies will suggest people who eat fish more often have a lower risk for dementia, compared to people who don't eat fish more options more often. So then the question becomes, is it the fish or is it something else about those people, they may have better diets, they may live in better neighborhoods, they may be higher educated and disentangling these things is very difficult. Then even if you can boil it down where you're confident that the fish consumption is really the driving factor here. Is it the specific omega three fatty acid in the supplement or is it something else about the fish, and again, even harder to disentangle? Unfortunately for fish oils, there's not a lot of great data to support supplementation with DHA for example, over and above a healthy diet is of any benefit. To me. It's much easier to recommend eating fish because we're not sure if it's the DHA or some other ingredient in the fish that might be valuable. And there are those epidemiologic studies to say that, in particular, people who really don't get enough fish could be at risk for negative brain outcomes later in life. I think the other thing I want to say is that supplements can have risks. That's why it's important to talk to your doctor. But I have seen a lot of even more risky therapies being offered to people, sadly, often very high out of pocket cash prices,


Steve 25:28

you're talking about interventions now. 


Josh 25:31

you know, miracles being sold to families, things like stem cell therapies, some cases direct injections into the brain of what what investigators might call mesenchymal stem cells, you know, that there are, there are a number of ways that individuals or organizations are again, capitalizing on the desperation that that patients families feel to find treatments. And, and some of these things have very real risks associated with them. And we've seen things like you know suggestions that this is a clinical trial, even to the extent of creating a clinical registration for something. Because that site is not extremely well regulated. People can create a page on that website and call themselves a clinical trial without really being a legitimate study. So again, talking to your doctor using trusted sources of of information, which I hope includes the UCI mind website, but also you can go to things like the National Institute on Aging's website, the Alzheimer's Association website, there are AARPs website, there are sources of information out there, the Internet can be a terrible source of misinformation. So people have to be extremely careful about vetting information, I would say at least once a week someone is sending me an email that's been forwarded to them about the next miracle cure for Alzheimer's disease. And as much as I wish we had a miracle cure to offer people. Right now if it seems too good to be true, it probably is. And I can assure your listeners that those of us in the space those of us doing this research will leave no stone unturned. We're willing to test anything that might have viability as a potential treatment, or diagnostic tool for Alzheimer's disease and other neurodegenerative disorders. But in the absence of this type of rigorous data, we just can't get behind these things and recommend them. And most of these emails with these miraculous discoveries, sadly, are often almost always too good to be true. So scrutiny is unfortunately the key seeking expert advice and understanding what if any evidence really supports what's being done. I think the other thing is, if it comes with a high price tag, if you're having to pay out of pocket, that's a warning sign. You know, again, an unfortunate parallel for my career has been seeing families spend 10 to $40,000 per year for things that simply have no evidence to support their use. And, you know, we'll see people combine things that have been tested in clinical trials have no evidence to support their use, but but, you know, suggest legitimacy because there's a publication that has tested an intervention, albeit without finding benefit of the intervention. So again, my my main message is, be careful. Talk to your doctor and find trusted sources of information so that you're, you're not throwing away money, you're not doing a GoFundMe page to pay for something that that probably has no evidence to support its using and could be harmful.


Steve 29:25

Well, that's great advice, Josh. If I wanted to do something, are clinical trials in participation and clinical trials, I mean, I know we do them at UCI mind, but this isn't there are lots of places that are doing reputable trials.


Josh 29:38

That's correct. There are lots of places doing clinical trials. And again, we're happy to talk to people about clinical trials, whether they're the ones we're doing or the ones that other people are doing. And it's important to say that, you know, this is the real opportunity to gain access to treatments before they're available. There is no guarantee that the thing being tested in a clinical trial is going to work. That's why we're doing the clinical trial. But the single most consistent barrier to moving forward as a field toward having these better treatments and having Prevention's is low rates of participation in clinical trials. And I actually think, you know, one of the ethical aspects of some of these other things is that people who might otherwise participate in clinical trials of potentially meaningful interventions are not doing so because they're doing these other things out of desperation. So, so yeah, there's all those same websites are likely to be able to point you to rigorous clinical trials of promising interventions, if something didn't have a promise, if we didn't think the science was strong, we wouldn't test it. And so if people are looking for better options, than what's available now, the best answer is to participate in a clinical trial. We understand clinical trials are not for everyone. Good Clinical trials are often placebo controlled. They're often burdensome, you know, we ask people to do a lot in clinical trials. And that's why the people who say yes, and who are enrolled in these studies at UCI mind are absolutely my heroes, I hope some of them are, are listening to this podcast, because we can't achieve our mission without them. Without the people who so selflessly give their time, their energy, put themselves at risk. You know, all drugs have risks. And they're really just an incredible group of heroes, who are joining us in this mission to try to find solutions for these diseases. And like I said, we can't do without them.


Steve 31:44

Yeah, I just add one comment from my own personal point of view, when you've been touched by this disease, which both Virginia and I have. That's the place to turn, you know, obviously volunteering, and donating. But also participating in clinical trials, you can help a lot, even if you aren't necessarily a candidate. At this juncture, there are other places for you to be involved. So any final advice you'd like to offer, Josh?


Josh 32:11

So my final advice is to be careful to always talk to your doctor before you begin taking anything as a treatment or supplement, to have trusted sources of information. And to be patient. I think it's an incredibly exciting time. I think that we are in the dawn of a new era in Alzheimer's disease, I think that we will have new drugs approved in the next 12 months. And I hope that that's going to position us to even further accelerate our rate of discovery, and changing the way we diagnose and treat Alzheimer's disease and even changing the way we think about Alzheimer's disease. And I think ultimately, someday, we will be looking for the opportunity to start treatments in people long before the memory problems begin so that people can live out their lives without ever developing dementia. And I believe we will see that in the coming years, especially if people join us in this mission by participating in studies.


Steve 33:18

Josh, thanks so much for taking time. I can tell you personally, this man is very busy. UCI mind runs a great number of clinical trials. And it's a pleasure and honor to be involved with such a great organization. So thanks, Josh.


Josh 33:35

Thank you so much. For having me.


Outro 33:37

Spotlight on care is produced by the University of California Irvine Institute on memory impairments and neurological disorders. UCI mind interviews focus on personal caregiving journeys, and may not represent the views of UCI mind. individuals concerned about cognitive disorders, prevention or treatment should seek expert diagnosis and care. Please subscribe to the spotlight on care podcast wherever you listen. For more information, visit