Aging with MS: Navigating the Journey

Aging with MS: Navigating the Journey

Episode 180 – Podcast Transcript

[(0:24)] Stephanie Buxhoeveden: Welcome to the Can Do MS podcast. I’m your host, Stephanie Buxhoeveden. I live with MS, and I’m also a clinician and MS researcher. Today we’re really excited to have a very special guest, Dr. Le Hua, who has been with the Cleveland Clinic for many years, where she plays a key role in clinical trials, assessing new therapies for the treatments of MS. Her research specifically focuses on aging and MS, exploring both medical and non-medical treatment options, as well as the critical role of cognition in managing the disease. We are absolutely thrilled to have her here to share her expertise and insights on how we can better navigate the journey of aging with MS. Welcome Le. Thank you so much for being here today.

[(1:03)]  Le Hua: Oh, thank you for having me. I think I’m, I’m excited about our conversation today.

[(1:07)] Stephanie: And today we’re gonna be talking about aging with MS. So can you tell us a little bit about how MS changes as we get older?

[(1:15)] Le: Certainly. Um, the most obvious change that we see, uh, with aging has to do with reduction in the inflammatory disease. And, and that essentially clinically manifests as, as, uh, people get older, uh, people with MS, they will have less relapses. Uh, and with that as a correlator that they will stop having MRI changes. That’s due to MS. We don’t see new lesions, and we certainly don’t see, um, enhancing lesions, uh, after a certain age. And up until you get to that certain age, it just reduces every decade until we don’t see changes anymore.

[(1:55)] Stephanie: Yeah. That’s definitely been my experience clinically, and, and as somebody with MS, I feel like I was having relapses and changes constantly, whereas now it’s sort of more of a slow burn, I would say.

[(2:06)] Le: Yeah. No, absolutely. And, and that change we see with that reduction in that inflammation, um, is, uh, in parallel we actually see an increase in what we call neurodegeneration or progression as, as what patients will, um, come to us and, and mention is that they’re just noticing that they’re worse. Um, and of course the common referring from your doctor is that, well, your MRIs are stable. And I think that dichotomy is really important to talk about because, uh, both can be true, right? Your MRIs are stable because they’re a marker of that inflammation. But the conventional MRIs, the typical MRIs that we get on a, a routine basis don’t show that underlying progression, which is the biological processes that’s happening for patients, um, uh, as the disease continues to advance. Um, some of those changes are driven, uh, by, um, changes in the immune system. Um, and some of those changes are also driven by changes in your, uh, endocrine system.

Uh, so we know that there are hormonal effects that lead to MS. Uh, we know that there are immune effects that then impact why the disease changes from something where we see these clinical relapses, [inaudible] changes to something that becomes, um, uh, more neurodegenerative. And, and those are really what we call, uh, immunosenescence, which is the aging immune system. And then also a concept called inflammaging, which is then inflammation or the immune system being disruptive and, um, causing more inflammation, uh, that drives, uh, the disability progression rather than this continual attack that we see with, that’s driving relapses.

[(3:57)] Stephanie: Yes, that’s super helpful, and I’m so glad you explained that it’s, you know, expected that at some point our MRIs don’t necessarily match up with what we’re experiencing with MS, and I know it can make me feel a little crazy sometimes ’cause I feel like I’ve gotten worse, but my MRI looks exactly the same, so I start questioning what’s going on. But your explanation of the difference being between inflammation and neurodegeneration and how MRI picks up one, but not the other, is something, uh, I know everybody would probably be very interested in. And so let’s talk about how that impacts treatments, right? So many people wonder whether they should keep the same treatment plan or make changes as they get older. So what should older adults with MS know about their treatments?

[(4:44)]  Le: I think it’s a, a question that we don’t have all of the answers to. Uh, what I always wanna emphasize is as we’re studying populations and we’re studying patients, we, we kind of know what’s happening at a very group level. But for the person in front of me, um, it’s difficult to then take these studies and this information and then say, what do we do for the person in front of us? Uh, essentially saying that there’s not a one size fits all, whether or not we’re evaluating should a patient continue with their disease modifying therapy, should they switch, should they stop, right? All depends on several factors. So our disease modifying therapies really target that inflammation that we’re talking about, those relapses and the inflammatory MRI changes as you get older because it, it’s not that you switch from [inaudible] the other. Both processes are present from the beginning, but as the inflammation decreases, the progression becomes more prevalent or more noticeable.

And our disease therapies don’t target that progression, those neurodegenerative changes. So the balance, that difficult question is in the person in front of me, how much inflammation are they demonstrating versus how much progression they’re, uh, demonstrating? And if they are more progressive and there really isn’t a lot of inflammation going on, then my disease modifying therapy is not going to help them. And then we need to focus on is my disease, is the disease modifying therapy hurting them? Meaning are there more risks that are increased because of age? And we absolutely know that, uh, because our disease modifying therapies all target the immune system and independently of that, as people get older, whether or not you have MS or not, your infection risk increases. So then you have this idea of do we continue to treat a medication that isn’t targeting the appropriate underlying process, but can certainly increase risk of other things going on?

And then that risk benefit rate ratio shifts. So if we have someone who is not having inflammation is really complaining about progression, right? And there may be other things at play such as, uh, their, uh, infection risk changes, then the therapy might be more harmful than helpful. Um, other things could happen. So as we get older, there might be new diseases that our patients pick up, and those new diseases can then be certainly contraindications for our medications. So, such as cancer, which increases with age, our medications might interfere with the cancer treatment or increase your risk of treatment. Um, and therefore that decision on whether or not to continue treatment while you’re undergoing, you know, your chemotherapy for cancer might then be something that we back up, back off on. Um, for patients who are feeling that they’re worsening on their therapy, it’s really important to emphasize that while our disease modifying therapies target relapses, there’s other things we can do to target the progression. So even if we might be stopping your disease modifying therapy, especially if you’ve been on it for over 20 to 30 years, there’s still other things we can do. So stopping the disease modifying therapy is not the same thing as stopping treatment for our patients.

[(8:10)] Stephanie: Absolutely. I think you explained that perfectly. Um, and how risk changes throughout our life and what works for us in one season of life might not work down the line. And it’s pretty normal to have to switch disease modifying therapies at some point in the disease course. So thank you for that really great explanation. Um, so treatment is obviously a huge piece of the puzzle, but aging also brings unique challenges for women, especially during and after menopause. So how does menopause affect women with MS?

[(8:41)] Le: Oh, if only [inaudible] had all the answers out there, so. So we are, we are actively learning, um, and understanding, um, the role of menopause, uh, overall, in terms of aging. So it’s a, it’s a, it’s a very hot area of interest, um, in the general population and aging in women, but all of neurological diseases as well. And it’s not really any different for MS. Um, the unique part about MS is the role of hormones throughout lifespan. So we know that, um, MS affects women more than men. Um, so the ratio tends to be, um, a three to one for the, um, onset of MS, but that really is tied to your, um, uh, hormonal curve. So puberty, right, pre menarche, um, uh, or the onset of menstruation for women, um, before that age. So if you’re looking at 10- to 11-year-olds, onset of MS is one-to-one. After puberty, that’s when we start seeing that three to one change.

And then after menopause is when the estrogen levels drop in hormonal, uh, hormonal changes occur in women, um, that ratio then approaches one-to-one again, right? So, there’s certainly something interesting about the role of hormones in increasing risk of MS. And then when they fall off actually complicating some of the symptoms and problems in MS. Um, we know that, uh, for patients, um, undergoing menopause, um, it can coincide with the time that we start seeing disability progression in women. And there are some interesting studies showing that, um, people who have what we consider like surgical menopause or earlier onset, um, uh, menopause or they never, they’ve never had children and therefore their[?] um, levels tend to be not as prolonged, those women who either have surgical menopause or, um, have never had children tend to progress faster. Like so they hit that progression earlier. Whereas women who have later menopause or, um, multiple children, so that then their hormone levels are kind of extended in, in, uh, for lack of a better, um, or a simplified explanation, um, they, their onset of disability progression for MS is actually, uh, slightly, uh, delayed compared to everyone else.

So we’re actively learning why that is, what those roles are and how that affects the underlying biological changes. Our understanding of the role of hormones in men is a little bit more complicated, so we don’t have that information as well. We know that men with MS tend to have lower testosterone levels. It might be associated with increased risk of MS, but it doesn’t tie to that disability progression the same way that we see menopause in women. Um, so, so very active area of, of research active, interesting, um, uh, uh, observations that we’re able to make. Um, and I think that should be an area that we focus on to kind of really better understand exactly what we do for, uh, menopause and how that impacts disability progression and MS.

[(12:09)] Stephanie: Yeah, I think that’s very true. I certainly know that the national MS society has prioritized aging and women’s health in terms of research. We’re also seeing a lot of research on the aging population in general, like how safe it is to stop disease modifying therapies, the impact of hormones. Um, so I think that’s a really exciting area of research and we will learn some more in the future, but there, there is still quite a ways to go in terms of our knowledge.

[(12:40)] Le: Yeah. And I think, uh, you mentioned hormones and, you know, uh, the obvious question is then, you know, what’s the role of hormone replacement therapy in our patients with MS? Um, uh, I think with that it’s also as women are undergoing menopause, some of those symptoms for menopause, um, might confuse MS, right? So if patients start having heat intolerance, right, or hot flashes, well, is that the heat intolerance that I already have? Or is my MS worsening or is this truly menopause that you know every, everyone else is suffering from? And, and those are the questions that, um, uh, become difficult to answer if we don’t have a clear-cut marker of this is MS, or this is menopause, or it’s both, it’s probably the answer that you end up getting. Um, uh, in addition to kind of just the temperature sensitivity, there’s cognitive changes. So within that, um, we know from other neurological disorders, especially like Alzheimer’s and everything else, that, um, cognitive changes do co-occur with menopause.

So those cognitive changes can, um, be even more noticeable for patients with MS or the cognitive changes they’ve already had might suddenly get worse and they worry about their MS worsening and progression. And the questions of whether or not hormone replacement therapy can help that or not is, is certainly one of those things that we definitely wanna explore and get better understanding of. Um, you know, some of those other things that we don’t talk about, you know, sleep changes that’s associated with, uh, menopause, uh, bladder dysfunction, sexual dysfunction, all of those are really critical aspects of quality of life as well. And if they’re all kind of occurring around the same time, I think that it’s safe to say that it’s probably likely menopause. And as long as there’s no risks to, um, uh, or contraindications to hormone replacement therapy, improving quality of life and treating that is, is always gonna be critical.

Hormone replacement therapy has, um, uh, specific risks. So talking to, um, your specific providers about your own risks, uh, risks of cancer, breast cancer, specifically ovarian cancer, um, and certainly, uh, risk of strokes and heart attacks become a very, um, individual question. Um, but so does being miserable, right? So, um, having, having the cognitive fog, having the hot flashes, um, becomes really important that we also maintain. And one of those other long-term risks that we don’t talk about is, uh, the role of like hormones with, um, osteoporosis risk, right? So patients with MS also have, you know, balance issues, high risk for falls, and if you add osteoporosis on that, um, then those risks become even greater. So, I, I think there’s lots of benefits to hormone therapies, not to, you know, belie that there aren’t also risks, but I think we need to kind of look at it from kind of a really lifespan picture, uh, in a moment, and then really weigh those difficult decisions. ‘Cause I don’t think we want anyone to be miserable and we don’t want anyone to have poor quality of life in the moment, um, for potential risk in the future. And yet those risks are real and, and important. And, and again, it’s, it’s all about that discussion and monitoring and making sure, um, that we’re really linked together closely to do everything we can to just improve the overall goal of quality of life.

[(16:10)] Stephanie: Absolutely. And you know, you’ve mentioned cancer and the incidence of heart disease, diabetes, this is something that becomes more prevalent as everyone ages, but the MS population is a little bit more susceptible to, to those comorbidities, what we call comorbidities, because it affects our mobility, it affects our ability to, you know, get up and move and exercise and do all those healthy things. Um, so what should people with MS be doing to sort of catch things or prevent other comorbidities? And could you tell us, just talk a little bit more about medications and, and other things that might become more of an issue as we age?

[(16:54)] Le: Yeah, no, absolutely. Um, it, it’s always, it know, it’s always interesting when I talk to patients with MS and they always really wanna just focus on MS. And I think sometimes, uh, providers fall in the trap of just MS, right? And then we kind of forget that there’s a whole person there and there’s all these other things. And, uh, sometimes our patients don’t tell us what’s kind of going on because they don’t think it’s related to their MS. And yet, you know, it’s one body. So everything’s, everything’s important. Everything becomes critical. When we’re talking about MS, specifically, the comorbidities that we call of interest are going to be vascular comorbidities because those have been shown to be associated with worsening MS outcomes. And when we mentioned vascular comorbidities, we’re always talking about the things that are associated with risk of heart attacks and strokes, right?

So, hypertension, diabetes, and cholesterol. And if, if we control those factors better, then the outcomes from MS are improved. Additionally, the outcomes from those risks of strokes and heart attacks improve. So it, so that’s definitely a benefit. We definitely see increase hypertension, diabetes, and, um, uh, cholesterol as you age, and then of course increased progression with MS. And if you already have one problem, you don’t really want multiple problems, right? That’s sort of how I tell my patients is that it’s important. With that smoking, right? So if we can get people to, uh, if you’re smoking to, to stop smoking really becomes critical. ’cause not only does it worsen those vascular outcomes, but it also worsen MS. Um, other comorbidities that impact MS that isn’t age related is actually depression and anxiety and mood disorders, um, are associated with worsening MS outcomes. We just don’t see that that increases because of age, but that it is really prevalent across all ages.

So, um, it is always important to reassess depression, um, anxiety, because that is also something we wanna treat. As we talk about treating though all these other symptoms, all these other, um, disorders, then you get into polypharmacy and, and that’s the idea that you’re on multiple medications. And the tricky part about being on multiple medications is that then they can start interacting and if they start interacting, they cause, uh, potential safety concerns. They can certainly contribute to being tired, uh, being fatigued. Um, and it’s always important then, rather than just adding on medications, making sure if taking off medications makes sense or can we treat multiple problems with one medication rather than multiple medications? So for my patients, we do review medications, review other medications. I won’t stop some of the medications from other physicians, but if there’s any medications I can stop from an MS aspect, we probably should.

With that of note, um, as we’re talking about our vascular issues, and we had mentioned earlier about whether or not to stop disease modifying therapies, some of our disease modifying therapies might actually worsen, um, vascular concerns such as hypertension. So certainly if hypertension is a problem and their medications are contributing to that, and it’s not really helping with your underlying, you know, relapses, but it’s actually causing worsening hypertension that can accelerate progression. So that would be actually a time to revisit whether or not the disease modifying therapy is appropriate and whether or not we should switch to something different or stop it.

[(20:33)] Stephanie: And I think that segues nicely into what steps people can take. And we already talked a little bit about this, but how to stay healthy and active and feel your best. Um, and the way I always put it to my patients and, and to myself is if you, if you treat the body right, the mind will follow, right? Our brain is very much connected, like you’ve mentioned to our cardiovascular system, to our gut microbiome. So our blood pressure, diabetes, um, all of these things, the food we eat, the cigarettes we hopefully do not smoke, all of these things do contribute to brain health and certainly to MS. So what are your tips for optimizing your wellness?

[(21:13)] Le: I, I think we cannot overemphasize enough the importance of exercise and it, it becomes really cliche, right? Um, so I don’t wanna fall into that trap of, oh, just exercise and everything will get better. Um, but we do have evidence showing that as you exercise, inflammation reduces, um, clear cut links with improving, um, uh, hypertension, diabetes and cholesterol with exercise. Um, uh, within that also just physical fitness, right? We talked about risk of falls, and we talked about muscle loss and everything else. So if you exercise, you can kind of build, um, some of that encounter the effects of um, that we know it’s, it’s happening, right? And we get weaker as we get older. We have increased [inaudible]. So the, the more you exercise, the more you focus on that, the less that becomes an issue and a problem. It’s training everything that we have to do.

Other benefits of exercise, it actually improves mood, it improves depression, it improves anxiety, it actually reduces pain. Um, so lots of benefits. So as we’re talking about, you know, a lot of multiplication, uh, medications and polypharmacy, one of the easiest things to institute that doesn’t become a medication that can actually help with multiple symptoms is exercise. With that, we absolutely understand how difficult it is for some people to exercise, right? Um, uh, motor fatigue is one of the biggest difficulties that our patients have. So it’s easy to tell you to exercise, but it’s also important that we say you need to exercise in a way that’s appropriate. So you might only be able to exercise for 10 minutes at a time, that’s it, right? Don’t push yourself, don’t overdo it, but maybe you can do it multiple times a day, right? So rather than one 30 minute or 60 minute period, maybe you can do 10 minutes here and 10 minutes there and 10 minutes, you know, at the end of the day.

And that consistency of exercise, consistency of physical activity is actually more important than just bulking it up once, being tired, exhausted, and never doing it again for the next week or so, right? So we want, we want consistent exercises. Um, I have patients who come in and, you know, they are wheelchair bound and then they don’t feel that there’s anything that they can do. And, and that’s not true. We can always, uh, find exercises that we can do despite, you know, whatever physical limitations you may have. So do we focus on your hands? Do we focus on stretching? Um, all of that is exercise, right? It doesn’t always mean running you, you know, marathons or running on the treadmills or riding the bike, but there are so many different forms of exercise. One of the things that I, um, I really want, um, my patients to really focus on as they get older is actually the core strengthening exercise is that’s gonna be critical, improve balance, and reduce falls.

That actually is those exercises that also help, um, uh, reduce some of the pain and fatigue that we notice. So, uh, for patients that are walking, I ask ’em, well, can they add a little bit more care exercises? Especially if they’re really great on their cardio, they might not be doing some of those other, um, aspects that we want them to do to really kind of look at, for MS itself, where do we anticipate your difficulties to lie? And here’s the exercise tools that really counter that. Um, and then you mentioned, you know, nutrition, diet, exercise, especially when you’re talking about the gut microbiome. So reduction in, uh, unhealthy foods, I guess would be the best way to say it. Um, some more fruits and vegetables, um, is what everyone could benefit from, and then less processed foods. And I think that’s the most generic of, um, advice out there, but it’s generic ’cause it works. And what I always tell my patients is whatever diet’s out there, whatever the fat exercise is, whatever the new, um, things out there, it’s hard to say, well, should I do this diet or this diet or this diet? And it’s like, well, rather than focusing on the differences, if you focus on the similarities, there’s a reason they all say the same thing, right? And they all say the same thing because that’s actually what works, right? So more fruits, more vegetables, less processed foods.

[(25:25)] Stephanie: Absolutely. I also emphasize especially as we get older and we have more symptoms and those symptoms can really make us more and more isolated throughout our lives, right? The importance of just getting out and having that social network and that group of people and that outlet, um, because isolation is a huge, huge detriment to health, especially in people with MS. And if you can do an exercise in a group setting, you’re sort of two birds, one stone or we just interviewed a, uh, best friend pair who makes meal prep their weekly social activity, right? So finding ways of taking care of your wellness, but also getting a little bit of social support, getting outta the house or having people come to you so that you’re not just sitting around by yourself ’cause it’s really not great for you in any way.

[(26:15)]  Le: Yeah, no, absolutely. It, it’s, um, it’s so true. Uh, by definition, human beings are social creatures, right? So we actually do need that. Now I always get the introverts who say, well, I don’t wanna talk to anybody. And yet you don’t wanna be alone, right? You don’t wanna be lonely. So, um, all those little types of conversations, the more we interact, the more we talk to people, uh, we really are working on our cognition, right? So how we speak, forcing ourselves to interpret body language, interpret voice, interpret changes, um, even if they’re just interactions with the cashier or you know, your server at the restaurant, um, even your medical personnel or things like that, those are all interactions that I would say count because they’re really valuable in terms of engaging that cognitive part of us and engaging those social benefits and those social wellbeing. One of the most devastating things that I’ve seen in my career is the impact of social isolation due to covid.

And we had significant people, and it was necessary for some of the social isolation that we talked about. And I think that sometimes our messaging doesn’t allow for nuance, right? So we definitely wanted people to, um, social distance, but we didn’t want them to just sit at home without seeking anything. And, and the messaging kind of got interpreted unfortunately in ways that were detrimental. And what I saw quickly was that, uh, our patients started having more cognitive problems because they were isolated because they lacked a routine, right? They didn’t have that same going to work. That having to get up and get dressed and get yourself, you know, prints for the day actually helps you feel better and helps you move. So that forcing of, of that, um, helps with cognition. And because people weren’t forced to do that anymore, they weren’t forced to ground themselves in a daily routine, we saw significant changes in terms of cognition. So absolutely, um, being socially engaged, being socially active is one of our best things to help with the cognitive concerns that we see as people get older.

[(28:26)] Stephanie: Yeah, that’s so interesting that you observed that. But the nice thing about covid is it opened up this world where we can virtually connect.

[(28:26)]  Le: Yeah.

[(28:26)] Stephanie: There’s lots of support groups and zoom meetups and those sort of thing. If, if you either live in an area without many resources in a rural setting where you don’t have an easy access to a gym where you could go take a group class or do an activity, then there are online options. Unless, but not least I sort of wanna shift back to research, right? And, uh, the fact that most of our clinical research is on younger people without any other health problems, because that’s what we wanna study medications in, is generally healthy people. Um, but that leaves a lot of unanswered questions for those of us living with MS for decades and do have additional health concerns. So how do you sort of bridge these gaps and provide guidance without that like concrete pivotal trial data?

[(29:24)]  Le: Yeah, so, um, we always talk in medicine about our gold standard of research, right? And our gold standard is always these large clinical trials that are randomized so that we know what happens with, um, one person, uh, versus another. And as in any experiment, if you think back to your high school experiments or grade school, whatever, you were exposed to it, um, you always only wanna just change one variable, right? So that you know that that’s the effect. Unfortunately, people are, you know, by definition messy, right? We don’t just have one variable with us. And so the clinical trials, um, uh, are actually excluding older patients because of safety concerns, right? There’s more things that are happening and we can’t prove that our medications work or don’t work or what safety concerns are if there, if it becomes like too many variables that we can’t control for.

Um, that being said, uh, we are pushing for increasing the age of our trials because we absolutely need to know, and there’s different ways to do trials. They might not be interventional trials. Certainly, as we develop therapies for progression of MS, we’re gonna want to look at older populations because that’s the population who, uh, also needs treatment and intervention. But outside of clinical trials, there’s always, uh, the reason why we have the data we have is through real world observational studies. And that’s where large academic centers, patients who are part of registries are really crucial and helpful, uh, because we’re able to then dig through data from patients and control for maybe some of those messiness comorbidities or treatments or everything to the best we can. There’s always some sort of, uh, statistical, uh, method for controlling for some of that. And then we can actually derive a lot of information.

So the stuff that I’ve talked about today in terms of, um, understanding immunosenescence and understanding inflammation and understanding the reduction in relapses in our activities, well those are all from observational real world studies, right? That’s how we got that information. So the data’s there. So for anybody who wants to be a part of MS research, actually seeing your doctor is always helpful, right? Because that data then becomes real world data that we analyze later. Uh, participating in registries. If maybe you’re in a more rural community and you don’t have an MS specialist that’s easily accessible, that’s participating in some of these, uh, uh, research, then there are national registries that you can be a part of. Uh, one of them is always the [inaudible] registry, uh, through the CMSC. Um, and that collaboration with the national society then becomes something that you can help, you can supply your own data to, and that allows us to then derive research and drive information out of it.

Advocating for that is always gonna be helpful. So I always ask my, uh, patients to help us with funding and help us with advocacy because, um, while I’m one vote, all of my patients then become multiple votes, right? So that’s sort of how we make ourselves heard that these are our priorities and they’re really important and it’s really critical that we understand aging, um, in MS specifically as the, um, prevalence of MS is shifting to older ages. You know, people over, over the age of 50 now make up more than half of the population of MS. Um, so it’s a very large group and it can be a very powerful group. And that power is something we should absolutely harness as we’re looking for more data, more information, more studies.

[(32:55)] Stephanie: Yes. Could not agree more. Thank you so much for all of your insights, your wealth of knowledge. Thank you for being here and for chatting with us about aging in MS.

[(33:05)]  Le: Absolutely. Thank you for having me.

[(33:07)] Stephanie: Thank you for listening to this episode of the Can Do MS podcast. If you like this episode, please leave us a rating and review on Apple Podcasts or Spotify. We appreciate your feedback. We’d also like to thank all of our generous sponsors for their support of this episode of the Can Do MS podcast. Until next time, be well and have a great day.

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