Search for tag: "disorders"

Interviewer: When depression or bipolar disorder isn't responding to standard treatments, they are referred to as treatment-resistant mood disorders.

Psychiatrist Dr. Brian Mickey from Huntsman Mental Health Institute's Treatment-Resistant Mood Disorders Clinic is an expert at treating these conditions, and today he's going to tell us how visiting a specialist can help people suffering from this condition live happier and more productive lives.

Dr. Mickey, first, when does a treatment-resistant mood disorder become classified as treatment-resistant?

Dr. Mickey: There's no kind of magic formula, but in most cases, we consider if you've had at least two adequate trials, meaning medication trials, psychotherapy trials, that are robust and that lasted long enough and you didn't respond, we would consider that treatment-resistant.

Interviewer: Either through medication or through psychotherapy, you would have to go through at least two of those. And if you weren't seeing an improvement of the symptoms, that would be classified as treatment-resistant.

Dr. Mickey: Right. Exactly.

Interviewer: Okay. When a patient comes to you after it being identified as potentially treatment-resistant, what are the interventions that you offer then initially?

Dr. Mickey: So some of the initial options that we would discuss would be changes to their current medication regimen. That would be a common one. Sometimes people haven't had an adequate treatment trial.

Another option that we would offer within our clinic would be transcranial magnetic stimulation. That's a non-invasive brain stimulation treatment.

We also can offer ketamine infusion therapy. That's an intravenous ketamine infusion that can be helpful for depression.

And so if these less invasive options aren't effective or cause too many side effects, then there are other surgical options that we sometimes will go to next.

Interviewer: Tell me more about the less invasive options. How long do you try those? How many of those do you go through before you kind of get to that point?

Dr. Mickey: That depends a lot on the particular patient, the kind of depression they're having, how severe it is, and, of course, insurance coverage. But typically for people who are functioning fairly well, they're going to work or doing their daily routines, then transcranial magnetic stimulation or ketamine infusion therapy can make the most sense.

Transcranial magnetic stimulation and ketamine infusion therapy are more compatible with maintaining your kind of regular daily routine and the side effects are relatively low for those as well.

For people who have had more severe depression that has been very debilitating or is preventing them from working, or let's say they're admitted to the hospital, then electroconvulsive therapy, or ECT, is what we would think of probably before those other treatments.

Interviewer: Are people intimidated by that name, the fact that you're using electrotherapy? I mean, that could sound kind of scary.

Dr. Mickey: Yeah, I think it can sound scary and if you don't know too much about it or if you only know what you've learned in the movies, then it's very scary.

Interviewer: And what happened like 100 years ago. It's not that anymore.

Dr. Mickey: Yeah, it's very different and it's a very safe treatment. It does have side effects and we counsel people about that, but it can really change the game for people with severe depression.

Interviewer: It sounds like you have a lot of options and tools at your fingertips to help somebody who has gone through some initial treatments and has not been able to handle the symptoms, take care of the symptoms in a way that they're able to go back to their life.

Tell me about a typical patient that walks into your office. Describe what that looks like and the conversation you have.

Dr. Mickey: So a typical patient that we see would come feeling pretty hopeless, I would say, because they've tried many different kinds of treatments and feeling like they've gotten to the end and they don't know what else there is to try.

Typically they've had years of illness, if not decades. And most people that we see also have had this illness since they were very young. So, most of the time, the onset of their illness is in their teenage years or young adulthood.

Typically, people are not able to enjoy life. They're not enjoying their work. They're not enjoying their social interactions. They become less interested in pursuing hobbies and being with other people. Most people have then become kind of socially disconnected, and that can even make things worse, because that's . . .

Interviewer: Yeah, and not finding satisfaction in work. Do these individuals realize that this is happening and are like, "I would love to find satisfaction in my work, but I just can't"?

Dr. Mickey: Right. Most people do, and the way they experience it is usually they're not sure why they're not enjoying it. And of course, we all have stress in our lives, but these are situations where the amount of sadness and mood dysregulation and loss of interest and pleasure is far beyond that. It doesn't make sense in the context. That's kind of what we're talking about here when talking about depression.

Those are the kinds of experiences and symptoms people are having before they're coming to our clinic. And what these treatments can do is they relatively quickly, within a few weeks, start to relieve people of those symptoms. And then the effects can last for months or sometimes even years before people will very often have a relapse.

And so that's something that we also educate people about. This is not a cure. It's a treatment that we can administer for this episode. But that can be a really meaningful difference for people.

Interviewer: And then if a relapse occurs, what then?

Dr. Mickey: For people who've had a recurrence, then we can oftentimes use these same treatments. And so we don't think of them as permanent fixes obviously. And so people will always have this kind of vulnerability. That would be the most typical pattern, that people have recurrences.

But if you understand the patterns, sometimes you can prevent them. That's the ultimate goal, is to prevent a recurrence. But if people do have a recurrence, then we can use these treatments again. And so those are the folks that we see and that I think we can help.

Interviewer: And for those individuals that have suffered for decades, what's the barrier to seeking out more treatment?

Dr. Mickey: There are a number of barriers. One is not knowing about what options there are beyond the things they've already tried. Another is oftentimes just insurance barriers.

Another barrier that people have I think is just fear of the unknown, kind of maybe not quite understanding what these treatment options are really like, which we can help educate people about that.

And then I think another is just that a lot of times people don't want to be a depressed person. It's not a great place to come from. And so you have to sort of admit that you have this condition before you're really going to come to the clinic. I think that can be a barrier as well.

Interviewer: Do you find it common that somebody that is suffering from a treatment-resistant mood disorder is not able to seek out help on their own and generally a family member is needed?

Dr. Mickey: It is pretty common. And I think part of it is that they may not want to think of themselves as a depressed person or they may not realize in some cases how severe things are.

And that's one thing that depression does, is it changes how you see yourself and how you think about the world. It makes you more kind of internally focused and less able to appreciate how far things have gotten in many cases. And I think sometimes people just don't remember how they were when they weren't depressed. So it has these effects on your own cognition and understanding of yourself, which kind of makes it unique.

Interviewer: You mentioned insurance can be a barrier for some people. Is there somebody at Huntsman Mental Health Institute that if somebody is concerned about "How am I going to pay for this?" that could help walk that individual through maybe some of the options if insurance isn't the option?

Dr. Mickey: Yeah, absolutely. In our clinic, we have referral specialists who will do all of those checks ahead of time and help you understand what the financial situation is. You don't want to go into a situation like this and not know what the cost will be. And there's nothing like an extra bill to accentuate your depression. So, yeah, that's an important aspect of the care that we pay a lot of attention to.

Interviewer: Well, it sounds like that you are offering hope to some people that have struggled with mood disorders for a long, long time. As we wrap this up, is there anything that you would say that you would like the listener to take away from our conversation today?

Dr. Mickey: Yeah, I would say that there is hope. And that's a very common reply or response that we get from patients at the end of a consultation. They're often saying, "I didn't even know there were all these options." It's pretty common actually for people to feel quite a bit better just after this single consultation visit before we've even administered any active treatments.

Newborns do a lot of strange movements and behaviors that quite often scare parents. What are normal newborn reflexes, and when should parents worry?

The first one most parents know and call the startle reflex. It's technically called the Moro reflex. Parents often tell me it's when their baby gets scared, but that's not really the reason. Babies don't get scared as newborns. It's due to their nervous system response to a sudden change in sensory stimulation.

And it's a good thing, actually. In fact, it's able to be seen on ultrasounds when a mom is only 16 weeks pregnant, and a baby's own cry can even stimulate it. It lasts until babies are about 2 to 3 months old.

So when should you worry? Well, if you had a difficult labor and there was concern that your baby might have had some oxygen deprivation, then an exaggerated Moro reflex could be concerned for something called hypoxic-ischemic encephalopathy. Basically, the brain is hurt by having the oxygen supply cut down.

Neurologists can help evaluate and treat this, and the good news is it's picked up really closely after birth. And if there's any concern, your baby will be in the intensive care unit really quickly for a full evaluation. If your baby is otherwise in the normal newborn nursery and goes home, there's a good chance this is not what your baby has.

Another normal reflex is the suck or rooting reflex. And that's just what it sounds like. It's basically what helps the baby learn to find a food source and eat. This reflex doesn't start until about 32 weeks of pregnancy, which is why preemies have such a hard time learning how to eat. This reflex is fully developed at about 36 weeks.

Now, when parents see this, they automatically think their baby is hungry and often that's true. It could be that it's just the reflex and they suck on their fingers and hands as a self-soothing behavior. I see a lot of parents trying to force their babies to eat and then the babies get over-full and throw up.

Then there's the tonic neck reflex. We call it the fencing reflex because they have one arm outstretched and one bent and they're about to say, "En garde!" Some parents worry that there is a problem because both arms aren't in the same position or both arms aren't being used the same way at the same time. But this is normal, and it can last until they're about 7 months old.

Finally, this isn't a reflex, but it's something parents ask me about all the time at the newborn checkups. It's called periodic breathing. Babies do this weird thing where they look like they're breathing really fast, then they can hold their breath for up to 10 seconds, and then they take a big breath in and then they're back to normal breathing. And it can happen when they're sleeping or when they're awake. And it usually lasts until they're about 6 months old.

Babies' lungs are still developing and their brains are still trying to figure out how to send messages to the lungs to remind them to breathe. Basically, they are still trying to figure out this whole breathing thing and breathing patterns. And it looks scary, but it's normal.

So when should you worry about your baby's breathing? If they're consistently breathing more than 60 times a minute, if they're having retractions where it looks like their stomach muscles are sucking in under their ribs, if they are making grunting noises with each breath, or if they hold their breath for more than 20 seconds and turn blue, those are not periodic breathing, and that needs to be evaluated right away to see if your newborn's oxygen is low. Depending on how severe the symptoms are, the best place for your newborn to be evaluated for breathing issues may be the emergency room.

One last thing. What about those eyes? Well, babies have very little control over their eye movements right away. That's why they always look at you cross-eyed. They're trying to figure out how to control their eye movements and learn to focus on things.

Also, it's not uncommon for a baby to roll their eyes when they're sleeping or when they're almost asleep, like when they're going to sleep or trying to wake up. But this should not be the norm. If they are not rolling their eyes but doing more of a rhythmic back and forth, something called nystagmus, that is absolutely not normal.

If your baby rolls their eyes often, that is not normal. If your baby's eyes roll and your little one also has stiffness in their arms or legs or has shaking that doesn't look like the startle reflex, that could be a seizure and that's an immediate trip to your local children's emergency room.

Many things can cause seizures in a new baby, including low blood sugar, low calcium levels, metabolic diseases, or brain abnormalities, in addition to epilepsy and high fevers. Your child will probably be admitted to the hospital and see a neurologist for tests to determine why they are having these weird movements and possible seizures.

So while a lot of these normal behaviors look concerning, they are often just part of your baby adjusting to being in the outside world. If your baby has any of the not-so-normal behaviors I talked about, please have them see their pediatrician right away or go to your closest pediatric emergency room.

Interviewer: The Aging Brain Care Program at University of Utah Health offers a range of services that help prevent, manage, and educate patients and their loved ones about memory and thinking disorders as they get older.

Dr. Michelle Sorweid is a dementia and geriatric specialist who works with the group. Dr. Sorweid, now there's a lot of different cognitive disorders. I think a lot of us laypeople just think of memory disorders, like Alzheimer's or dementia. So why don't you walk us through some of the things the Aging Brain Care Program can help with?

Dr. Sorweid: Yeah. So the most common question that I get is, "What's the difference between Alzheimer's disease and dementia?" And I try to use kind of a picture or imagery of an umbrella. So the comparison I use is actually cancer or kind of a broad term. So dementia meaning folks who've had decline in memory and thinking in one or more areas over time and that has impacted their day-to-day life, meaning they might be needing help with things like managing their medications, managing their finances, there might be errors in driving, things like that. And so Alzheimer's disease is the most common cause of dementia, and so that's why it often gets overlapped with one another. But there's quite a few other causes, as you mentioned, things like Parkinson's disease and things in that family of conditions. There may be blood vessel disease causing someone's symptoms. And there's quite the spectrum, you know, before someone reaches a dementia syndrome or qualifies for that diagnosis. There may be symptoms that are consistent with normal aging or something we call mild cognitive impairment. And so that's kind of the spectrum we look at and help diagnose and determine, you know, what's the cause and how can we intervene to prevent decline.

Interviewer: You mentioned diagnosis, which is generally, in a lot of conditions, the most important thing, is to figure out actually what's going on, and it could also be one of the most challenging things. So a specialty clinic like this, how can you make a diagnosis more efficiently, more effectively, more accurately?

Dr. Sorweid: So just like when someone comes in with a cough, we usually need more information to figure out how we can treat that cough or how we can manage it. And so it's a little trickier because we're talking about the brain. But we do a pretty thorough physical exam and history, just as with any patient coming in with specific complaints. I usually like to have a brain MRI, because that's how we take a picture of the brain. It's the most specific way to look at it. And then we usually do additional, more objective testing. So if someone, you know, comes in with a specific complaint and symptoms, we don't necessarily just rely on that. We need some objective information. So we usually do a screening assessment and then, depending on the situation, might refer them to much longer, you know, three or four hours of memory and thinking assessments.

Interviewer: And after you have the diagnosis, then you would move on to what can be done about it. And as a layperson, my perception is, a lot of times, there's not a lot that can be done about it because it's part of the aging process, and once the cognitive decline starts, I mean, there's really no stopping it. There's no cure.

Dr. Sorweid: Absolutely. It's a common misperception that having memory changes is a part of the normal aging process, and though it is common, it is not normal. And so that's one common misperception, that memory changes are not necessarily a part of the normal aging process. And then, in addition, another common misperception is that there's nothing that can be done, and unfortunately, a lot of physicians have perseverated that misconception. And so, unfortunately, we're kind of working with an uphill battle because a lot of that has pervaded throughout the medical community as well. And that's why I kind of mentioned earlier is better. There's more we can do from a standpoint of intervention the earlier we know symptoms are developing. So that includes things like managing blood vessel disease risk factors, like high blood pressure, high cholesterol, sleep apnea. There's a lot of different conditions that we know we can treat and, therefore, prevent decline or slow decline.

Interviewer: So like physical conditions that could be causing that.

Dr. Sorweid: Absolutely.

Interviewer: Oh, okay. Well, that's encouraging because that's something that, you know, one could take care of.

Dr. Sorweid: Exactly. And so that's one piece of the puzzle. But the other piece is that a lot of families and patients aren't really well prepared for some of these changes, and knowing the diagnosis really helps us help them plan for their future, know how much financial impact this might make, know what to do as far as treatment goes, because the treatment varies depending on the diagnosis. And you may have heard in the news, there actually recently was a disease-modifying drug approved in early Alzheimer's disease. So we are looking at more and more options for treatment of Alzheimer's disease specifically.

Interviewer: And at the Aging Brain Care Program, you have a lot of different individuals that can help support that family, not just physicians and neurologists but also social work support and psychiatrists as well. How do they play into helping somebody that has a cognitive disorder?

Dr. Sorweid: Absolutely. So we have a social worker who helps provide both disease education and helping manage the expectations of families and patients as far as, again, you know, what is this disease going to look like, what do I need to prepare for. So she does a great job at supporting these families and ongoing management. We also have our geriatric psychiatry nurse practitioner who is amazing. And, you know, we know that depression is a very common symptom that goes hand in hand with a dementia process or cognitive disorders. And so she's a key player in our team in helping manage these patients.

Interviewer: And what is your ultimate hope for a patient that comes into the clinic when they leave? What would be the ultimate best outcome for you?

Dr. Sorweid: I think just kind of dissuading these common misconceptions that we discussed, is that we can do something to help them, that there is hope, that they are well supported, that they don't just get a diagnosis and scooted out the door, but that they have a team on their side to help support them through this journey.

Interviewer: It seems to me, you know, the purpose of a lot of health care is to improve quality of life or maintain quality of life. How important is that to what you do, and what does that look like?

Dr. Sorweid: Absolutely, and that's kind of the common theme in geriatrics, specifically, is that quality of life is our most important goal.

Interviewer: And what does quality of life for somebody who has some sort of cognitive disorder, a memory or thinking disorder look like?

Dr. Sorweid: That's an interesting question. I think that's a very evolving question and very patient-centered, meaning that may be very different for any one individual person. That might change from year to year or month to month even, and that's something that's kind of a moving target for a lot of people. So it's something that we have an ongoing discussion with patients and families about.

Interviewer: So the Aging Brain Care Program, is it just for people who have already started noticing a decline in their cognitive abilities, or could a person come in and access your services that would benefit them before issues start to arise? Say, you know, they have a family history and they suspect that that might be an issue in the future, and they want to be proactive about it.

Dr. Sorweid: I've certainly seen patients and families who have a strong family history of dementia or who have some mild symptoms that they've noticed, and perhaps all of their screening turned out to be more of a baseline or normal, and so that is an option. I think, traditionally, that's not typically who we see in our clinic. It's mostly patients who have had some symptoms even though they may be mild. But the key thing that I would focus on with regards to a healthy aging brain is that a lot of these interventions really play a role even in midlife. So we know now that there's data that shows controlling blood pressure, even to possibly a more aggressive level, can actually help prevent mild cognitive impairment or mild memory changes.

Interviewer: When you start to recognize cognitive decline, at what point should you really consider coming into the Aging Brain Care Program? At first outset? Because, I mean, some of us can feel really weird, you know, if it's just one thing or a couple of things. How do you help a patient navigate that thought process?

Dr. Sorweid: I would really encourage at the very onset of any symptoms to seek help. Worst case scenario, you're seeking help earlier than what is needed, and, I mean, that's a good thing. Then we have a baseline. And really seeking help early, again, just kind of focusing on those interventions that we know are helpful can really make a difference in someone's quality of life, whether or not they are aware of what's to come. You know, if a loved one is complaining of, "Hey, I misplaced my keys," or "I'm forgetting names more often," there's a chance that's due to normal aging, but there's also a chance that something else is going on, especially if it's a change for them.

Interviewer: Do you recommend that somebody go to their primary care physician first, or when they start recognizing these symptoms, is it just better to come to the Aging Brain Care Program first?

Dr. Sorweid: I think if someone has a really great relationship with their primary care provider, they know them well, they're already established with someone, that is a really great place to start. There's something called the Medicare Annual Wellness Visit, and that provides all primary care physicians the opportunity every year to screen for a lot of different conditions, including cognitive disorders. And so that's something I would encourage patients to ask their provider to use as far as a tool to screen them for any problems with memory and thinking. And then, yeah, so next step or if they feel that their primary care provider doesn't feel comfortable with any of those screening assessments, then, yes, we're happy to see them.

Interviewer: And we're really fortunate to live in the Salt Lake City area and have access to University of Utah Health and the Aging Brain Care Program. How can individuals who are not in the immediate area access this great resource?

Dr. Sorweid: One of the silver linings of the COVID pandemic is having access to telehealth, and so that's one opportunity that we have to offer visits for our patients who maybe are limited by distance or who have a difficult time physically getting to the clinic. It's not ideal because there's limitations with physical exam or if they have difficulty, as many of our older adult patients do, with a video exam. But generally speaking, they're with a loved one who can help with that, so that's one opportunity. And then just to keep in mind that many of these visits aren't super frequent. It's up to the patient to how often they come to see me or one of our other providers.

Interviewer: Yeah. And a combination of perhaps those ways of visiting might work out too, I'd imagine. Maybe the initial visit is in-person because, you know, you can facilitate more of the types of physical examinations that you need to do, and then more of the follow-up visits could be virtual. Dr. Sorweid, if patients are in the Salt Lake area, where are you located, and what is the best way to reach you?

Dr. Sorweid: Located on the main University of Utah Hospital and Clinics campus, just at the corner of Mario Capecchi and Foothill, 555 Foothill Drive. And our clinic phone number is 801-581-2628. Just asking for a referral from your primary care provider would be appropriate, but we also take self-referrals.

Interviewer: If you or a loved one would like more information about the University of Utah Health Aging Brain Care Program, you can find a link to their website included in the description of this podcast.

Dr. Clardy: Hi, I'm Stacey Clardy, Associate Professor of Neurology at the University of Utah. I'm excited today to talk with Stefan Pulst for our series on where cures for brain diseases begin.

Stefan is the Chair of Neurology here at the University of Utah and has accomplished a tremendous amount in that role. But today I want to focus our discussion on his role as a very successful researcher in neurodegenerative diseases.

Specifically, Stefan, you are quite well known internationally for your work on a group of conditions called spinocerebellar ataxias. How did you find yourself focusing on this group of diseases? They are rare diseases. Did you seek out that area based on a lecture you heard early in your career or a patient you had seen? Was there some sort of existing project? How did you settle on the spinocerebellar ataxias for your particular research questions?

Dr. Pulst: Well, it was a typical L.A. story. I was Chair of Neurology at Cedars-Sinai at that time, and I got a phone call, a phone call from a colleague at UCLA, who recalled that, as a resident at Columbia University, he had seen a family that had a very unique distribution of age of onset of a particular neurodegenerative disease. It appeared to happen earlier and earlier in each subsequent generation.

And it's hard to believe today, but in the late '80s, I was one of the few neurology geneticists in Los Angeles. So that's why he called me. And I said to him, "I've never seen a genetic disease that I don't like," and we decided to fly out to New York State and examine that family, obtain DNA samples. And then my search began to find the actual mutated gene that caused this disease that we now call SCA2 or spinocerebellar ataxia type 2.

Dr. Clardy: And this is sort of unique and really, I think, drives home the point of the value of a clinician scientist, right, because you're both a scientist but also were able to come see the patients. You're a physician. You're able to examine them and get a sense of what was different about this, highlighting, I think, what's unique about academic medicine is that you serve in both those roles. And, of course, that was pre-Zoom era, so you had to fly out there.

Dr. Pulst: We had to fly out there. And we learned a lot from the patients. Part of cerebellar disease is that you are uncoordinated in your gait. And so one of our measures was to ask people to basically walk a line, like a police officer would do when they pull you over. And we had one young woman who we asked to come back and do the test again. And she was very concerned that she might actually have inherited the disease. And we later found out that she did. She was just a bit clumsier than some of her other family members. So when one learns a lot, and I think that, you know, I've been in this business now for 40 years, what I enjoy about it, going back and forth between lab and the patient and then back from the patient back to the lab, asking the questions.

Dr. Clardy: And you just hinted at what I was going to ask you next, which is how long have you been studying this condition? I think we somehow read a news release about an exciting research finding and we think that it happened in the last six months. So tell us when you started. How long has it really been?

Dr. Pulst: So we flew out to Syracuse, New York, in the late '80s and collected DNA samples. And then, for the next six years, we tried to identify this gene. And although this can be much faster today, this was a time where the genome was not mapped. We made different kinds of maps, maps based on distance and on location. And finally, in March 1996, we identified the disease gene that is now called ATXN2. All the ataxia-causing genes have numbers now. And we found out that it was a very unusual mutation, actually a mutation that was dynamic. It did not remain stable, and in the end that explained this phenomenon of having earlier and earlier disease onset in subsequent generations.

Dr. Clardy: And so what I heard you say was it took a long time to find the mutation. So what have you been doing on that mutation in that ensuing 25 years? Right? You get to discover what the problem is, and then what's next?

Dr. Pulst: Yes, and quite right. We thought climbing the Everest was finding the gene. That there was a lot of glory to be had to find the gene, and then somehow the therapy would just fall into our lab. And now we just know that we were in the hills leading up to Everest. Everest was really finding therapies. And for really a decade, maybe even two decades we and others spent our time trying to understand what this disease gene actually normally does, assuming that, when it's mutated, it has something like a deranged normal function.

And really, for me, the change came with moving to Utah in 2007. We decided to completely refocus and target the mutated gene itself. After all, that's the first cause, the primary reason why patients develop this particular disease, a DNA change happens. And we thought, if we can somehow quiet this disease gene down, then we would have a path forward. And that's what we have been doing since 2007. And you're quite right, that is still 13 or 14 years ago, and it has taken us that long to develop a gene-directed therapy.

Dr. Clardy: Wow, that's incredible. And I want to back up a little bit before we get to talking about the therapy that you're working on. The mutation you found, tell us more about this class of conditions, the spinocerebellar ataxias. What do all the patients look like? Are they similar? Are they different? How many different types are there?

Dr. Pulst: Yes. So the patients with ataxia share a certain presentation. Most of them present with gait instability that then progresses to affecting their speech, their reaching movements, their stance, their eye movements, and sometimes also their thinking. So these are really neurodegenerative diseases. They share some features with other diseases, such as Huntington's disease, but also with diseases like Lou Gehrig's disease or motor neurone disease. So they really fall into the larger group of neurodegenerative diseases.

We have about 50 SCAs, spinocerebellar ataxia, so at least 50 genes or gene locations that cause dominantly-inherited ataxias. These diseases are called polyglutamine diseases because a repeat that normally codes for the amino acid glutamine, it now expands and causes very large stretches of glutamine that misshape the protein, misform it. It tends to aggregate and cause disease.

Dr. Clardy: So unlike some other neurologic diseases that are caused by, say, missing a piece of a chromosome or a deletion, in these spinocerebellar ataxias, most of them, it's really all the DNA is there, but there's extra and it's repeated. Is that right?

Dr. Pulst: That is correct. It's repeated and it's repeated in a part of the gene that directly codes for a protein, so it has a direct effect on the way this protein is formed, the way it behaves. And as we now know, these repeat expansions cause the proteins to aggregate and really cause havoc in the cell.

Dr. Clardy: And I think what you're not saying is that a lot of this was not known. And certainly 50 different types were not known when you started this area of research. And you're saying that family had SCA number what?

Dr. Pulst: Number 2.

Dr. Clardy: Wow, so early on.

Dr. Pulst: Yeah, actually, in Utah, we are working on finding the mutation for a disease that is very common in Utah. It's called SCA4. So it was mapped to a chromosome a long time ago, but it has been very difficult to find the actual mutation causing that disease.

Dr. Clardy: So SCA4, the fourth spinocerebellar ataxia to be discovered is actually common in Utah. I didn't know that. Can you tell me more?

Dr. Pulst: Yes. So this disease was originally described and mapped to chromosome 16 by a former faculty member here at the University of Utah, Dr. Kevin Flanigan. And when we came, we took this off and we realized it is a family, a gigantic family, with more than 1,000 members actually. And we traced them back. The individuals were early pioneers. Actually we know that they were born in the 19th century, came from Scandinavia to Utah. And it's a disease with late onset, so people have a normal number of children. And we have now mapped the disease more precisely to chromosome 16.

What we have also found out, that other families, that we became aware of, there's a smaller family in the U.S. state of Georgia, and we were able to map them genetically but also by family records back to southern Sweden. And we actually found out that the family in Georgia and the family here in Utah come from two villages in southern Sweden that are about 10 miles apart. And there appears to be even a link between them, a man who was an oiler, he oiled machines and he may have had relationships in these two villages.

Again, it's a neurodegenerative disease that affects mainly the cerebellum, so patients have uncoordinated gait. But, interestingly, it has other effects as well. They develop a very significant sensory neuropathy. So what that means is they cannot quite sense where their toes and ankle and their fingers are. So they really have to deal with double damage. Both the feedback from the joints is not correct, and then the part of the brain that should coordinate all this information, the cerebellum is also defective. We are now pretty certain that it's not a simple mutation. It is likely a complex rearrangement on chromosome 16 that has made it difficult to pinpoint down what the precise mutation is.

Dr. Clardy: Wow. So just one of the other . . . I know we only touched on a couple areas of research in your lab, but this is obviously another one. And I love so much of what was in that story. One, the power of genetics, that we can trace back history now. But, two, I think you and I talk about this frequently, both being sort of transplants who came here to work at the University of Utah, but just the power of the recordkeeping and the ancestral records and the Utah population database, how the original settlers continue to give us information to push the science forward. It's such a fun part of working here in Utah.

Dr. Pulst: Yeah. And to give our listeners a bit of a visual image, usually, when you draw a family tree, a pedigree, you know, it fits on a sheet of paper quite easily. In this SCA4 family, we have like a papyrus scroll because it is so enormous. And actually, when we unroll it, it goes across my office. It's quite remarkable. And it was really thanks to one particular patient who contacted family members and made this pedigree. And it extends from Idaho and Wyoming all the way to Arizona through Utah and to California.

Dr. Clardy: That's fantastic. And we have so many of those patients here who are really driving their own science. It's wonderful, right?

Dr. Pulst: Yes, it's great. And the family is very involved, and we owe it to them to find the genes. So we are trying to work as hard as we can on using some of the most modern gene-sequencing technologies. And at this point, as of today, we have not found the mutation. So we still need to examine more patients and hopefully narrow also the location on chromosome 16 even further.

Dr. Clardy: Wow. So a lot of areas of research going on in your lab. I want to switch back a little bit though. You started to allude to this. Your lab has developed what's called an antisense oligonucleotide as a therapy, potentially, for one of these types of spinocerebellar ataxia. And, as I understand it, this has actually also led into a potential treatment for Lou Gehrig's disease or amyotrophic lateral sclerosis. But can you tell us what is an antisense oligonucleotide and how might it work in this disease?

Dr. Pulst: So this goes back to the refocus on targeting the actual cause of the disease, the primary cause. And that's the faulty gene that then leads to a faulty molecule that we call "messenger RNA." It's a molecule that takes the message of how to make proteins from the nucleus into the cell body, into the cytoplasm, and then specifies how a protein is made.

So, as I said, there's an expansion of a DNA repeat, which means the mRNA, the messenger RNA is expanded and the protein has an expanded polyglutamine domain. So we thought, "Why don't we try to attack the faulty messenger RNA and make a molecule that is complementary to this messenger RNA, it binds to it?" And then, what the cell does is actually, when it sees a new molecule made out of a messenger RNA and a piece of DNA, it actually targets this new artificial molecule and destroys it. And that's really the basis of these antisense oligonucleotides. They're called antisense because they are complementary antisense to the messenger RNA. And the oligonucleotide just means they have between 18 and 22 base pairs, so they're much shorter than a long messenger RNA.

And then, when this happens, an enzyme comes in, chops up the messenger RNA, so it's not present anymore. The antisense oligonucleotide is released and can undergo another round of binding to messenger RNA. So, with modifications, these new molecules are very stable and can be effective for therapy.

Dr. Clardy: And if I'm understanding what you're explaining correctly about this mRNA approach, this could really potentially be used in people who are known to have inherited the mutation but aren't yet having symptoms. Is that right?

Dr. Pulst: Yes. Yes, that's actually our hope for genetic disease to target diseases as early as we can. It just makes the point for our listeners that it's important to ask your neurologist to really get to the basis of a disease, to get to the correct name of the disease. And sometimes that means being referred to a specialist who really lives with these diseases and knows a lot about them.

Dr. Clardy: You make a really great point there, which is it's one thing to treat the symptoms, but perhaps the strength of the University of Utah or other academic medical centers too is that while we're treating the symptoms, while we're addressing where the patient's at, we also want to know what caused it in the first place. And your lab is, obviously, one of the extreme examples of that where you've actually found the mutation. So what phase of trial or study is this antisense oligonucleotide in right now?

Dr. Pulst: Okay, let me step one step back because it's important to realize, when I said that these ataxia sometimes are really neurodegenerative diseases that affect other nerve cells as well, and we recognized, just by seeing patients, that some of them had characteristics of Lou Gehrig's disease or amyotrophic lateral sclerosis. So, clinically, we saw that there appeared to be a connection between SCA2 and ALS. A colleague and friend of mine at Stanford, Dr. Gitler, then discovered molecularly a link between SCA2 and ALS.

So when we drove the development of this antisense oligonucleotide to ATXN2 forward, we partnered with a pharmaceutical company called Ionis and developed this initially in mouse models of ataxia but also in mouse models of ALS. And this molecule, the best one we identified in mouse studies and in studies in non-human primates, has now gone into a Phase I trial in ALS patients. And the reason it's in ALS patients, this is a more dramatic disease, very often, unfortunately, leading to death in three to five years, in some patients even earlier. And there are more ALS patients than SCA2 patients. So the dose finding study, knowing how much of this ASO to inject, is done in ALS patients. And a few patients have been injected so far with this new compound.

Dr. Clardy: It is very exciting, and it is really . . . you know, the neurodegenerative diseases are sort of the last frontier in neurology, right? They have, historically, hit a wall when it came to trials. And it sounds like your work and obviously the work done in other conditions and using antisense oligonucleotides is really the most exciting thing to come around in our entire generation.

Dr. Pulst: I agree. I think it's remarkable that really this dream of finding the genetic causes of disease actually now is leading to therapy. And I think another point is that even if you work on rare diseases or very rare diseases, if you pursue it, you may obtain insights into more common neurodegenerative diseases, as this connection between ALS and spinocerebellar ataxia type 2 shows.

Dr. Clardy: Well, I know certainly when I see patients in our shared clinics who have a neurodegenerative disease, I really love telling them that, just down the hall, you're doing work on this and you're making progress. But I want to know what advice do you have for patients who are diagnosed with neurodegenerative diseases?

Dr. Pulst: I think the first line of advice is try to really find out what your neurodegenerative disease is. Does it have a name? Does it have a genetic cause? And that often requires to go to specialists or sometimes, as I call them, sub-specialists or sub-sub-specialists who really know about the disease. It is still true that there are actually very few ataxia specialists in the nation. And patients fly to Utah as they do to other ataxia centers to find the right diagnosis.

Genetic testing these days is less expensive than getting an imaging study. And insurance companies are slowly learning that it's the right way to go and to support these tests.

The other general piece of advice is be part of clinical trials. I think we know that patients do better when they're in clinical trials, even if they just "get the placebo." So you get to see specialists. You get followed up. People take great care of you. So I think that's the other one.

Dr. Clardy: Well, thank you, Stefan. Again, I've been speaking with Stefan Pulst, our Chair of Neurology here at the University of Utah, on his groundbreaking work on spinocerebellar ataxia and the possible translation over to amyotrophic lateral sclerosis as well. To learn more about his research, to support the lab, or any of the many, many research projects and labs here at the University of Utah, you can just go ahead and google "University of Utah neurology" where you'll find links about all of the ongoing departmental activities and information on how you can become involved.

Interviewer: You've noticed a change in your teenager's mood. They're angry, moody, defiant, irritable, and in addition, their school performance or maybe interest in other activity is significantly decreased. You're worried about depression. Is it okay to talk to them about it, or could it cause more harm than good?

Dr. Thomas Conover is a psychologist at University of Utah Health, and what is your advice for parents about how to talk to their teens about these tough topics? Or should they even talk to them about them?

Dr. Conover: Communication is a real key. It certainly is protective and helpful for parents to communicate and inquire with their teen as to what's going on and how they're feeling. And that's something that I think most parents strive for but may struggle with. How do I talk to my teen? What do I talk to my teen about? Is it okay to ask? I would advance to say that it's always okay to ask your child about how they're doing. You seem really sad lately. Is there something bothering you? Is there any way I can help?

Interviewer: No. I mean you probably have to dig a little bit sometimes, huh?

Dr. Conover: You may. I think that there's value in setting an example and leaving the door open by saying those two things. In terms of setting an example, certainly communicating openly oneself is important. Right? So I've talked about various areas of function that a parent might look at for a teen child and use to try to evaluate how serious a problem that they're suspecting maybe. But a parent can show that those things are important themself. Right? A parent can demonstrate that being engage with social activity and self-care and physical activity, you know, which boosts mood, all of those things are important. So a parent may set the stage in their own family by doing those things.

It's always okay to ask your child about how you're they're doing. And even though a lot of times teens may seem outwardly like they don't want someone to ask, I think most of the time people who are struggling even in a small way do want someone to ask. I think it's helpful not to badger. I think if you're met with that initial no on a first inquiry, it's good for a parent to perhaps say, "Well, okay. You know, I hear that you're saying that there's nothing about it that you want to talk about. But just know that I'd be happy to talk to you if you do . . . if you change your mind about that, if you do want to talk about."

I think that's a tough one. It's a tough balance to strike, because I think if a parent is a concerned at all about their child and they try to make that initial ask, first off that's a hard thing to do. You know, you might be thinking about it all day or all week and then, finally on Friday you say, "Oh, we're sitting at dinner and my kid's actually home with me. I'm going to ask." And then, the first thing that they snap back with this, "No. Everything's fine." And the parent might feel kind of rejected by that and, you know, they might respond by shutting down. Right? Going like, "Oh, well, okay. I guess I shouldn't have asked."

I wouldn't advocate for that black and white of a response, nor would I advocate for a parent then saying, "Well, no, I know something must be wrong. I've been watching you all this time, and you just aren't acting yourself. You need to talk to me right now." You know, in most cases, that's not going to be the best approach either. It's, I think, always appropriate to ask and it's always appropriate to maybe give a little space and a little time for the teen to be able to absorb the question and respond. Now, that would be with the exception of a true emergency, and those emergencies do include threats or acts of self-harm or threats or acts of a suicidal nature or serious aggression.

Interviewer: Are you concerned that your teen might be suffering from depression? Now, sometimes it can be difficult to tell the difference between moodiness and actual depression, and that moodiness can be common in a lot of teens.

But psychologist Dr. Thomas Conover says you should look at how your children are doing in what he refers to as key life areas. That's school, extracurricular activities, social, and family life.

Dr. Conover, let's just start with school. Why is school performance one of the clues that you use when evaluating children for depression?

Dr. Conover: For teens, school is their primary area of function. It's, in my mind, equivalent to holding down a job or a career for an adult, right? And so if an adult is still functioning in their primary vocation, then that's a good sign. Same way for a teenager. If he or she is still doing well in school and not seeing a decrement there, then whatever is going on with the teen, you've got some reassurance that things haven't gone completely south.

Interviewer: What about extracurricular activities? Some kids just aren't into school, or don't necessarily perform well in school.

Dr. Conover: Well, I look for their performance in school with comparison to earlier performance too. So if you have a kid who was somewhat of an indifferent student and just wasn't that academically inclined throughout their school life, kind of a solid B/C student, then that's what I would be looking for the child to be doing going forward. So I'm not concerned if there's sort of indifferent performance when that's been the norm.

It's really looking at, "Has that gone downhill?" Do you have a child who normally got straight As and is now getting Bs and Cs, or a child who normally gets Bs and Cs who is now failing or having incompletes? That would be more concerning in terms of school performance.

And for those youths . . . let's say you have a child who's an average student and maintaining that performance, but who is an avid athlete, plays a sport year-round, and is withdrawing from that. That could be a concern as well. So looking at function in the academic realm is important, but there are other areas of function too, right?

So other activities are very important to look at. Social function. A normally developing or typically developing teen is a very social creature. It's a time of life where you're learning how to be independent, and you're transitioning in typical development from being reliant on your family as a primary source of your activities and values to your peer group, which in my mind and experience serves as somewhat of a transition to being fully independent. Having your own ideas about things, your own values, your own priorities for your activities.

So, in that vein, your typically developing 15-year-old is going to really want to be out there and socializing with peers. A lot of times, nowadays, that does take place over cellphones, social media, and the like. And so it's important to take that into account, that just because a teen isn't going out all the time doesn't mean that they're not socially engaged.

But a parent can reasonably expect that their teen is going to be interested in what's going on out there with their peers. And if they're more withdrawn or less interested in that than they used to be, that's a concern.

Then there's also family function, and it is normal and expectable to have a teen be less interested or less enthusiastic about certain family activities than he or she used to be. That is normal and expectable.

Then I would go back to the idea of, "Well, just how pervasive and intense is it?" Do you have a teen who says, "I don't want to go to family dinner at grandma's this Sunday. My friends are going out. I want to meet up with them," but who ultimately you can cajole and negotiate and get the teen to do it? Or do you have a teen who has a big blowup over that and ends up leaving the house and you don't know where they went? I'm giving fairly stark examples, but the gray area in between can be evaluated.

I haven't mentioned the threat of self-harm, or aggression, or worse, suicide. That would be an obvious red flag. If inquiry into a teen's mood or a parent making a request or demand of the teen leads to any sort of threats or acts of self-harm or aggression, then that's something that a parent would want to seek help for urgently.

Interviewer: Moody teenager or depression? When is the time to seek help? That's what we're going to find out today.

Dr. Thomas Conover is a board-certified child and adolescent psychiatrist. He is also board-certified in general pediatrics, and he has taken care of teens with and without depression for over 20 years.

Dr. Conover, when a parent comes to you or walks up to you or sees you at a party or something like that, and they say, "Dr. Conover, I've got a question for you. I've got a teenager. I'm a little bit concerned," what kinds of words do they start to use to describe their concern with their teenager?

Dr. Conover: You'll often hear about moodiness or irritability, being more isolative than usual, simply not wanting to do things with the family the way that they used to. Those are some of the most frequent keywords that parents who are concerned about their child's behavior or mood as a teenager will say to me.

Interviewer: And when you hear those words . . . certainly, when I hear those words, I think, "Well, that's a teenager." Right? So is it a little difficult to determine when to be concerned and when not to be concerned?

Dr. Conover: It sure is. Even as a practicing psychiatrist all these years, if I hear a parent say that their teen is moody or irritable, I don't immediately jump to the assumption that he or she is depressed.

Interviewer: So then you would, I would imagine, start asking some questions, trying to get a little bit more information. What are some of those questions that you would start to ask to start to make the decision whether or not there was something to be concerned about?

Dr. Conover: One question is, "How long has it been going on?" That's a common question in medical inquiry in general. Another is severity. Just how bad of moodiness or irritability are we talking about here? I always think too about how is the youth functioning. That's a really important thing.

So particularly, in a casual setting, if a parent just asks me a question about their teenager, a lot of times I'll ask, "How are they doing in terms of their other life pursuits?" So if a youth seems to be more moody and irritable but he or she is still doing all the things that they would normally do, still functioning in school, still recreating with friends, still engaged in other activities, but just kind of crabby, I'm a lot less concerned.

Not unconcerned, because there are some youth or adults too who are suffering but still managing to eke out their function because it's that important to them to do well in school, or with their sports, or whatever else they do. But I am often reassured if a teen is still doing the things that he or she normally would do despite the apparent problem with mood.

Interviewer: At what point does a parent say, "You know what? We should go talk to somebody"? When does it become something that a parent can help? Because it would occur to me that any of these little symptoms would be something you might want to talk about anyway. If the grades are starting to fall, you might want to approach that topic. If they're defiant a lot more, you might want to say, "I've noticed a change in . . ." Or maybe you don't want to say it like that. Help me out.

Dr. Conover: It's always okay to ask your child about how they're doing. And even though a lot of times teens may seem outwardly like they don't want someone to ask, most of the time people who are struggling, even in a small way, do want someone to ask.

I think it's helpful not to badger. I think if you're met with that initial "no" on a first inquiry, it's good for a parent to say, "Well, okay. I hear that you're saying that there's nothing about it that you want to talk about. But just know that I'd be happy to talk to you if you change your mind about that, if you do want to talk about it."

It's, I think, always appropriate to ask, and it's always appropriate to maybe give a little space and a little time for the teen to be able to absorb the question and respond.

Now, that would be with the exception of a true emergency, and those emergencies do include threats or acts of self-harm, or threats or acts of a suicidal nature, or serious aggression.

Interviewer: So we have a pretty good idea of some of the different behaviors we might see that might indicate that a teen is depressed or heading towards depression. We've learned that the first step really is to try to talk about it and be genuinely concerned and not force, not corner. If you get met with some rejection, give the teen some space. At what point then does a parent seek professional help if they're just so frustrated, they are convinced something is up, and they just don't know what to do?

Dr. Conover: The primary care provider is equipped with enough training and understanding about childhood and teen depression to help to evaluate that and may then refer on to other resources.

Interviewer: I feel my approach would be I'd want to find out even more information. Maybe I might want to go to a professional on my own before I take the step of involving the teen in the process, because I'd be afraid that maybe doing that would somehow damage our relationship or cause problems. What's your take on that?

Dr. Conover: My take on that is twofold. On one hand, I think it's perfectly reasonable for a parent to seek education or support from other resources themselves. An initial inquiry in that fashion might mean that the parent would do some reading. They might get online and go to a reputable source such as the websites for the American Academy of Pediatrics or the American Academy of Child and Adolescent Psychiatry, both of which have really good information about child and teen development and kind of the presentation of various problems and resources for how to respond.

It might take the form of talking to a family member, a friend, a clergyperson, or the parent's own physician. All of those could be things that a parent could do.

On the other hand, I do think people may make the mistake of not asking, not saying something, not doing something for fear that it might damage the relationship. And it has very rarely been the case in my experience, even if asking or stating that observation leads to a fight or argument in the short term.

Interviewer: As that parent that asked you initially if they should be concerned about their teenager walks away, what would be the last thing that you would say to them?

Dr. Conover: "Let me know if there's more help that I could give." You can go off in one direction, make a decision to act, and maybe that initial effort comes up not as fruitful as you had hoped. So I would hope that people would feel open to asking for help again or talking more about it.

But it can be an uncomfortable topic. My experience both as a clinician and as a parent myself is that parents want their kids to be happy. They want them to feel okay. And it can be very, very troubling, very sad to contemplate that their child may not feel okay, that they might not be all right. And so it's really hard to ask and really hard to bring up, because you don't want it to be so.

This content was originally created for audio. Some elements such as tone, sound effects, and music can be hard to translate to text. As such, the following is a summary of the episode and has been edited for clarity. For the full experience, we encourage you to subscribe and listen— it's more fun that way.

As many as 1 in 5 adults in the U.S. are dealing with a mental illness including depression. Depression and anxiety can be very difficult to identify. Feelings of sadness and anxiousness can be healthy, normal emotional responses to events in your life. Depression can be both a symptom of another illness or an illness in and of itself, so it can be difficult to draw the line.

Dr. Kyle Bradford Jones experienced the struggle firsthand. He experienced a lot of pressure and anxiety during his time and medical school. He had long hours without sleep, poor eating habits, no exercise and, as a physician, dealt with the decisions of life and death. It was a slow build over many years that led to his clinical depression.

He eventually reached his turning point after experiencing a serious panic attack. The "awful, terrifying" experience led him to seek professional help and eventually take medication to help work through his depression. Medication Can Help Get You Out of the Rough

Often, a positive change in diet, sleep, and exercise can help a person through a run of mild depression. But sometimes, the symptoms of depression can be a major hurdle to improving one's lifestyle. Many patients may benefit from a short-term prescription that can help get those habits back in place.

"It's night and day," says Dr. Jones, explaining how much his life has improved after starting medication to treat his mental health. He explains that he was able to get his desire, passion, and drive back. "It's not just getting back to the way things were; it's about being your most successful, best self."

For most patients, medications to help treat depression and anxiety are not long-term. Many patients are on medications for only a short time. Also, recognize that finding the right type and dosage of medications can take time before you start feeling the positive effects. When You Should Get Help

There is a fine line between the negative emotions of anxiety or depression, and clinical diagnosis of clinical depression. Your primary care physician should have the tools and training to make a professional diagnosis and make further recommendations as needed.

If your relationships are being impacted by a chronic emotional state, or if your feelings are acting as an impediment to living your life, it's worth reaching out to get help.

Common symptoms of depression include:

• Lack of enjoyment in things you used to enjoy
• Sleep too much, or sleep too little
• Feeling guilty about the inability to function normally
• Lack of energy or motivation to complete tasks
• Suicidal thoughts

If you are experiencing any of these symptoms, consider reaching out to your doctor for a diagnosis.

If you are experiencing thoughts of suicide and need immediate help, call the Utah Crisis Intervention Hotline, 801-587-3000 ER or Not: Rolled Your Ankle

Producer Mitch recently rolled his ankle badly during a run. It hurts and is very swollen. Should he be running to the emergency room for treatment?

According to Dr. Madsen, most rolled ankles hurt and can look pretty bad, but do not require emergency attention. Unless there is a bone sticking out the ankle is seriously misshapen to, an urgent care can provide all the treatment necessary. Another option is a walk-in orthopedic clinic like the one at University of Utah Health.

There's a protocol used to identify whether or not an x-ray is necessary for your injury called The Ottowa Ankle Rules:

1. Can the ankle bear weight?
2. Is there tenderness on the ankle bones themselves?

If you are unable to stand on the ankle, or if there is tenderness in the two bones that stick out on either side of the ankle, it's time to get an x-ray at an Urgent Care.

Otherwise, you can treat the injury at home with ice, elevation, and an ace bandage compress. Odds and Ends

The Who Cares About Men's Health 5K has been moved to June 20. We encourage anyone who wants to join this virtual race and show support for Mitch as he gets closer to his goal of going from couch to 5K. The virtual race can be completed any way you'd like, whether it be running, biking, walking, skipping, whatever you can do to get in your physical activity that day. Stay tuned for our updates for the event.

This week you can visit our Facebook to get your 5k race bib. Download and print the file so you're ready for race day. Take a photo of yourself in the bib and post them to the Who Cares Facebook page or using the hashtag #WCAMH5k to show your support. Just Going to Leave This Here

On this episode's Just Going to Leave This Here, Troy finally was able to go for a run without snowshoes, which - as far as he is concerned - marks the end of winter.

Meanwhile, Scot finds himself looking at his phone while he's walking. It's happening much more frequently lately. He's thinking that humanity will have to come up with some way to make sure we don't bump into something. Talk to Us

If you have any questions, comments, or thoughts, email us at hello@thescoperadio.com.

Interviewer: It's a conversation we're not used to having or starting. I'm talking about planning for end-of-life care, and if you are planning for end-of-life care because of a diagnosis with Alzheimer's or other sort of dementia, it becomes even more complicated whether it's for yourself, or whether it's a loved one that has that diagnosis.

So to help out with that process, we're talking to Kara Dassel. She's in the Gerontology Interdisciplinary Program in the University of Utah Health College of Nursing. And her research team has developed this thing called "The LEAD Guide," which stands for Life-Planning in Early Alzheimer's and Dementia. So everybody should have an end-of-life care plan. But from what I understand, if you have Alzheimer's or some sort of dementia, that end-of-life care plan is going to look a little different. Explain why that is.

Kara: There's more of a time crunch in a broader context within Alzheimer's disease or other types of dementia where there is a limited window where you're able to engage in your family member with dementia and learn about their preferences and wishes before they get too cognitively impaired where they're no longer able to have those conversations.

Interviewer: Wow. So after the diagnosis comes in and you find out that maybe a loved one or even yourself has dementia, how soon should that conversation start?

Kara: The earlier the better. It shows that you have better care outcomes as far as having your medical decisions match your preferences if you have those discussions and document it. You're less likely to be hospitalized if you don't want to be. You're less likely to be shuttled in between nursing homes and hospitals and rehab facilities. And it's a better outcome for the people making the decisions for you because they don't have the burden of trying to guess what mom would want.

Interviewer: When it comes to advanced care planning, I thought this was interesting. I tend to always think of just medical preferences, like this is what I want medically done or not done. But it goes beyond that. And "The LEAD Guide" is based on what you call value-based decisions. Explain what that means.

Kara: Yeah. So sometimes just checking a box of whether you want a ventilator or not doesn't give you the full context of end-of-life values and preferences. And in dementia, in particular, someone may be physically very healthy but lack decision-making abilities. And so you need to make decisions about if they need long-term care, is that going to happen in the home? Is it going to happen in assisted living, a nursing home? You needed to decide where their location of death is going to be, because with dementia people live on average 8 years after diagnosis, but they can live up to 20 years. And so there's a lot of care decisions and medical decisions that need to take place within that long death trajectory.

Interviewer: So this can be a tough discussion to have. So I guess I'm thinking from the perspective of maybe a family member wanting to bring it up after that diagnosis. Are there other reasons why it's just really important to have that discussion? Again, it's not a discussion we're used to having.

Kara: Right. Not a discussion you're used to having, and I think just knowing that your window is limited puts the time pressure on having these discussions within a context of progressive dementia. And I like to frame it with families as it is beneficial for the person with dementia and the family members to have this discussion for two reasons.

One, the person with dementia has the comfort and peace knowing that they were able to communicate what they want currently and then also what they want when they have advanced dementia. That might differ. They may want something different today versus five years from now when they're in a nursing home. And so being able to communicate that can bring a lot of peace and comfort to the individual.

And then also, family members can approach it as, "Do me a favor. I want to carry out your values and preferences, but I need to have this conversation with you in order to do that." And that would relieve a lot of burden or guilt or disagreements among family members. So it's really a service to the family to have this conversation.

Interviewer: I was surprised to see in the research that you and your team did to make this guide that, for some people, the emotional burden can last months or even years, the caregiver emotional burden.

Kara: Right. If you're in a situation where you really don't know what your husband or partner wants, or mom or dad and you have to, it's an acute situation in the hospital and you have to make a decision, you may question whether you made the right decision for years. There might be a lot of lingering guilt and stress of not knowing.

Interviewer: Yeah. So I'm looking through the guide here. What I really like about it is it seems pretty simple. And this is a point where I want to say this does not replace, if I understand correctly, an advanced directive. This is not an advanced directive. This works with.

Kara: Right. This is a supplemental guide that's not legally binding, but it provides additional information about a patient's values and preferences and some of those questions that are unique to dementia, like location of long-term care and preference for location of death.

Interviewer: It starts out with a little checklist of the end-of-life documentation that you should have, which is great because that can get confusing. So I like that. And then when you start getting into some of these end-of-life value questions, I found this fascinating because I think we put ourselves in the situation by not having these conversations. Like the very first question, I'm concerned about being a financial burden to my family or close friends. For my mom, like I would spend the money to continue to make her live if that's what she wanted. But then how often is there a disconnect that that's not actually what the person wants?

Kara: Right. And so a lot of these questions here about values, they help inform decisions. So if you know that your mom is really concerned about being a financial burden, then that will help you make decisions about her care in the future. And the same with being an emotional burden or a physical burden. You know, if your mom's really concerned about burdening you physically with day-to-day care tasks, then maybe that makes you feel a little more comfortable about placing her in a 24-hour skilled-care facility when that time comes, knowing that that's your mom's value.

Interviewer: Have you seen this actually in action?

Kara: Yes. So we have . . . A part of the process of developing this guide, we held multiple focus groups with healthy adults, caregivers of people with dementia, and people with early dementia themselves. And the feedback we got was very valuable about, "Wow, this is great. I hadn't thought about this." Or, "I never knew mom cared so much about not dying at home." So it really raised a lot of questions that they hadn't discussed before.

Interviewer: Yeah, that's fantastic. Is there anything else that we need to talk about this? I think this is such a fantastic tool, especially for somebody . . . You know, I know what we need to talk about. We need to talk about somebody with dementia, not only just the deterioration after the diagnosis, but end-of-life wishes tend to be different for patients that know that they're going to have dementia versus maybe somebody that knows that they're going to have cancer.

Kara: The dementia preferences were different from those other ones as far as not wanting medical treatment interventions in a situation of dementia versus cancer. And then, having a preference not necessarily to die at home, being more comfortable dying in a nursing home or at the hospital. And so a lot of the qualitative data that we got showed that the loss of sense of self, of independence, of memory really defines quality of life. And people didn't want to extend that type of life in general.

Interviewer: Understood. My last question is this is such a great tool. Is it something that anybody could use for planning end-of-life, even if it wasn't Alzheimer's or dementia? Because I know it was specifically designed for that, but could it be used for other cases as well?

Kara: Of course. So people may lose the ability to make decisions at the end of life for a variety of reasons, due to other medical conditions, head trauma. So you can use this guide to help with any sort of advanced care planning. It's just meant to facilitate the conversation.

updated: April 29, 2022
originally published: May 13, 2020

Interviewer: We're here with Dr. John Rolston, the Director of Functional Neurosurgery, and Dr. Matthew Alexander, he's an Assistant Professor of Radiology and Neurosurgery here at University of Utah Health. Let's start with just kind of talking about essential tremors. What is an essential tremor and what does that mean for patients that have it?

Dr. Rolston: So essential tremor is the most common movement disorder that anyone in the world has. So it's a movement disorder characterized by uncontrolled tremors or movements of typically the hands, but sometimes the voice and head too. These movements are pretty common around eight times per second when they happen, and they can start disrupting people's lives. So with a really bad tremor, it's hard to do things like sign your name, write checks, hard to eat or drink from a glass, hard to eat soup with a spoon. It can become so disabling that people are unable to do these activities at all. And that's when they start to, and before them, when they start to approach us for medical treatment or surgical treatment.

Interviewer: And so you're saying eight times a second? Is that all day long?

Dr. Rolston: All day long, all the time, except when you're asleep when it goes away. But when you're doing any sort of activity, it's there and prevents you from doing all these normal things you used to do like talk on the phone or type on a keyboard.

Interviewer: And what causes it?

Dr. Rolston: We don't really know yet. So even though it's the most common movement disorder, the amount of research that's been done for it is far dwarfed by the amount that's been done with other diseases like Parkinson's. So we're still trying to find out the underlying mechanisms for what causes it. But we do know that it's definitely involving circuits in the brain. We know this because changing how these circuits function can improve the tremor, which is the basis of our surgical therapies for a tremor.

Interviewer: And Dr. Alexander, when someone comes with an essential tremor, how do you diagnose it? What do you look for? What do you . . .

Dr. Alexander: So it's fairly obvious to us by the time they get to us, but it's usually a progressive disease that has gone over the course of decades. There can be familial variants. So some people experience this starting their 20s, 30s. I've heard of some people even in their teens. Most people, it's, you know, middle-aged folks start to notice it. And it's usually just kind of a tremor that they have in their hands. They might notice it gets a little worse with intentional movements. But it's a progressive disease. And so they'll notice over years that it gets worse and worse and worse. And so by the time they get to us, because we only treat the most advanced cases, it's a pretty easy diagnosis to make. And it's often been made by someone in the community, either a primary care physician or someone in neurology that that patient has been referred to.

Interviewer: And Dr. Rolston, after you have the diagnosis, you're seeing these people, they have this really debilitating tremor in their lives, what is the way that it's typically treated or used to be treated?

Dr. Rolston: Sure, that's a great question. So the way we typically start treating these patients is with medications. So there's only one FDA-approved medication for essential tremor, and that's propranolol. The brand name is Inderal. So many patients are prescribed this if they can tolerate it, if they're not forced out by the side effects of low pulse, dizziness, lightheadedness. Then, they can go and take this medication, and it might reduce the either frequency of the tremor or the amplitude of the tremor, so basically how much it's affecting them.

There's other drugs when that one doesn't work. There's another drug called Primidone, which is very common. It's actually an anti-seizure drug. This one also has a lot of side effects, so dizziness, tiredness, that a lot of people can't tolerate. Once those two medications have failed, there's a lot of other more experimental drugs people try. But when the first two primary drugs fail, the chances of one of these third or fourth-line therapies working is pretty low. And that's when surgical therapy becomes more of an indication.

Interviewer: What is the typical way of doing the surgery? I mean, we're talking brain surgery, right?

Dr. Rolston: Yeah. So they've known since the 1950s that if you go to these small little parts inside the brain . . . they're called the ventral intermediate nuclei of the thalamus. So there's two of these. They're both pea-sized little pieces of tissue deep inside the brain, kind of toward the middle of the brain. There's one on the left and one on the right.

If we damage either one of these . . . We noticed, back in the '50s again, that there was a substantial improvement in the tremor on the opposite side of the body. So if you injure or get rid of this left-sided one, you can see an improvement in the tremor on the right side and vice versa. The way we used to do that was with an open brain surgeries. We would make a hole in the skull, insert a fine needle, heat up the tip of the needle, and burn out this small little pea-sized area. This worked great, but it involves a hole in the head, which is a big deterrent for a lot of people to seek this therapy.

Interviewer: Understandably.

Dr. Rolston: Yeah. In the 1990s, they developed a deep brain stimulation, which puts a wire in the same location, but instead of damaging that part of the brain, it stimulates it electrically with a pacemaker that sits in the chest. And that's very effective. And that's what we've been mostly doing for the past couple of decades now.

Interviewer: But it's my understanding there's this new ultrasound-assisted . . . what is it called?

Dr. Alexander: MR-guided focused ultrasound. The MR is for magnetic resonance, so like an MRI machine, which is actually where we perform the surgery.

Interviewer: Inside the big tube?

Dr. Alexander: Yes.

Interviewer: Wow. Okay.

Dr. Alexander: So they go in an even smaller tube, the thing goes inside that big tube. So this utilizes the opportunity of ultrasound to be able to deliver energy to tissues in the body. So we normally think of ultrasound when it comes to diagnostic imaging, so maybe for like an obstetrical ultrasound, to look at a fetus, or maybe if somebody has gallstones, they look at the gallbladder that way. And that involves a diverging set of little sound waves that are sent out from a probe. And then, that bounces back and gets interpreted and spit out by a computer on a screen to look at an image inside the body.

We've known for a long time that each of those little sound waves can cause a little bit of energy to be deposited in the tissues. In those diagnostic scenarios, it's very safe. Again, they're diverging and it's a small amount of energy. We know that we can focus these beams much like using a magnifying glass with the sunlight. And we can use that to actually effect change. We deposit enough energy that we raise the temperature and burn that little pea-sized area just as they did back in the '50s but without actually making an incision.

Ultrasound, it's the same technology that underlies those imaging studies that people get, but it's a different way to harness that energy to use over 1,000 elements to deliver a bunch of very small things. And so you get them all converged at one area. It actually delivers a fair amount of energy. And so we go through several steps of imaging to map out where this VIM nucleus of the thalamus is using an MRI. And then, we also have a CT scan that kind of maps the skull, and then we overlay that with the MRI. And using that CT of the skull, we can direct the ultrasound to make sure that we target it precisely where we need to get.

Interviewer: Wow. And how long does the whole process take?

Dr. Alexander: So the whole process is probably about three to four hours. Part of that is spent shaving the head, getting the frame on. The actual part where they're in the scanner is probably anywhere from an hour and a half to three hours. Probably more often on the hour-and-a-half range though at this point.

Interviewer: And then what? Do you just send them home? Are they stuck in the hospital for a while or . . .

Dr. Alexander: We observe them for a little bit, make sure there are no side effects. They've gotten some of those medications. And then, there will be a little bit of swelling in the brain that makes them a little uneasy, a little wobbly. So we observe them for an hour or two, but it's an outpatient procedure. They go home that day.

Interviewer: Dr. Rolston, how long have you guys been doing this?

Dr. Rolston: So we've been doing this for about a year now. It's been FDA-approved for slightly longer than that. So we're the only place that does it in this time zone in the United States, so the only center in this region. We've had a great experience. So the patients that we've done have had fantastic outcomes.

When they did the randomized control trial to prove that this was effective, they had about, on average, a 50% improvement in the tremor. But that included patients that . . . The way they designed the study was called an intention to treat. So there were some people that didn't actually get treated that are included in that 50%. So the results, they were probably a little bit better than that. We're seeing results that are better than that still. So more like 75% or better improvement in the tremor for all the patients we've treated.

There's some thoughts and considerations we put into selecting patients. We want to make sure that they obviously have essential tremor before we do this procedure. But there's also a consideration for how dense the skull is. The skull is a big component of how we do the therapy. We try to do the therapy through the skull with the ultrasound, but sound waves travel really well through solid, dense things, but less well through kind of mushy, less solid things. So you can kind of imagine knocking on a table, and that has a nice loud echo, but if you knock on a pillow, you don't get much sound through that.

So we need to make sure the patient's skull is very dense and able to conduct these sound waves to cause the changes we're looking for. And we do this with a preoperative CT. So we get a CT scan the day before or a month before. And we measure the density of the skull to make sure that we can actually have a successful therapy. And there's some people, especially with bad osteoporosis, where we can't get the result we're looking for. So those patients, you could perform the procedure, but you might not get enough temperature increase to cause a permanent change.

The most important thing about this is we've had good surgical treatments for tremor for a long time, but many people are understandably worried about doing any invasive surgery, any sort of incision anywhere. Now that we have this non-invasive treatment, even though there are some limitations based upon skull density, some limitations on the kind of person to be best for, even though we have that, it's a wonderful new opportunity to bring people in for a treatment that otherwise would never consider any sort of invasive therapy. So there's a large population of patients that would never be able to be treated that can now be treated, which is why we have such a tremendous response to this and so many patients that are interested.

Interviewer: This seems like a technology that could be used in a lot of potential ways. What do you think the future is for this?

Dr. Alexander: Absolutely.

Dr. Rolston: Yeah.

Dr. Alexander: So it's a fantastic new tool, and we're looking for ways to apply this tool. So there are new trials that are currently underway for other things such as Parkinson's disease, mood disorders, things like that that will be on the horizon in the coming years. But then, in addition to that, and part of what's exciting to be doing this at the University of Utah, is we're looking to further expand indications. So we are working with some of our basic science and translational researchers here on campus to use animal models to try to develop new methods, new things that we can use this to tackle. And so it's a really exciting opportunity, both to be able to offer this new, really effective treatment, but also be able to try to expand the horizons so that we could offer it for, you know, a lot more people for a lot different diseases.

Dr. Jones: It is really dark in the morning these days. Fall has beautiful colors and the days can be gorgeous, but they're getting short. Are you sad about that?

Announcer: Covering all aspects of women's health. This is The Seven Domains of Women's Health with Dr. Kirtly Jones on The Scope.

Dr. Jones: Shorter and darker days in the northern latitudes affect mood for many people. About 1 in 20 people experience seasonal variation in depression, with fall and winter showing a rise in depression. Of those people who are affected with seasonal depression, four out of five are women. This condition has been called Seasonal Affective Disorder, appropriately shortened to SAD syndrome or Seasonal Depression.

In the extremes of latitude up near the Arctic Circle, the winter is associated with increased risks of suicide and the summer with light all day, and night has been associated with increased mood, even euphoria, really increased good mood. Symptoms of SAD include feelings of depression, worthlessness, low energy, and lack of interest in things you usually like to do. Other symptoms and behaviors are a sense of fatigue leading to oversleeping. Spending longer times under the covers with longer, dark days is common. Some women describe carbohydrate cravings, which if you give way to eating those Halloween candies and Christmas cookies can lead to fluctuating levels of glucose which can complicate mood stability and of course can add to seasonal weight gain, which is depressing.

Symptoms start in the fall and get better in the spring. This problem was independent of income and lifestyle factors. According to the National Institutes of Mental Health, the main risks for seasonal effective disorder are age, sex, history of depression, and distance from the equator. The condition seems to start in women in their 20s and 30s.

Why women are so much more likely to be affected isn't well understood. Some researchers have suggested that reduced sunlight can affect serotonin levels, a brain hormone that affects mood. Fluctuating estrogens, which women have and men don't so much, also affects serotonin. Also melatonin, a brain hormone produced in the dark can increase in dark days and adversely affect our sleep-wake rhythm. It can upset our circadian rhythms, which can be associated with depression. So if this is you, what to do?

Number one is phototherapy or bright light therapy in the mornings, and this has been shown to be effective in decreasing symptoms in up to 85% of women with Seasonal Affective Disorder. Now, this is really bright light, brighter than any light bulb, especially now with our new light bulbs. Special devices that deliver 10,000 lux. Lux, L-U-X, is a measurement of light. They are not very expensive and can be bought on the web for about $50 to $100, and some are more expensive than that. Make sure that the light box is designed to treat Seasonal Affective Disorder. You can search light box for Seasonal Affective Disorder and add 10,000 lux to the search term.

This bright light is like medicine. It can suppress melatonin, so it should be used in the morning. Sit about two feet away from the light box for 20 to 90 minutes while reading or doing some work. The light is bright, but don't put your sunglasses on. The UV light that might damage your eyes has been filtered out with these light boxes, so the bright light doesn't damage your eyes. If you find that you're getting out of bed later and later in the fall, using morning bright light therapy will help reset your biological clock so you can get up earlier.

Number two, go outside and get some natural light. In most of the western U.S., we have lots of light in the winter. It's often cloudier in the northeast and the north central states, so it can be harder to find natural, bright light, but just getting outside and going for a walk can make people feel better.

Number three, exercise makes you feel better. Even when it's the last thing you want to do, make an appointment with a friend or a kid and get some exercise. Regular exercise, especially early in the day, not before bedtime, has been shown to help regulate circadian rhythms, which can be important in treating SAD.

Number four, eat this, not that. Try to limit the sugar swings associated with high carb foods and sweets. This is the time to eat your protein and veggies. If you aren't getting enough vitamin D in the winter, which most of us won't because we live in northern cold climates and bundle up, leaving nothing exposed to get our natural vitamin D, you can get vitamin D naturally in fatty fish like salmon and in eggs. Some studies suggest that people with SAD are low in vitamin D and omega-3 fatty acids. Increasing sources of these in your diet is good for your heart and your brain anyway.

Number five. If you know that you're vulnerable to depression and decreased mood in the fall and winter months, get started early on activities and interventions that can help. Don't wait until the darkest days of your mood. Bright light therapy and planned diet and exercise changes early in the fall.

Six. My favorite recommendation is to change your venue. Go south, visiting climates that have more sun. Of course, this can be expensive and disruptive to the family, Thanksgiving and Christmas if mom bugs out to take a holiday on the beach, but it's just a thought. Of course, cranking up the heat in the house, getting a beach blanket and your shorts and sitting in front of a $50 light box is much cheaper, but not so much fun.

Finally, and importantly, this fall and winter holidays can be stressful for women. If you're already struggling with depression, substance abuse, anxiety and the dark days are making it worse, reach out for help to family, friends, and your clinician. You may not believe it in the dark days of your mood, but we can make it better. I'm off to dig up my light box. Thanks for joining us on The Scope.

Announcer: Have a question about a medical procedure? Want to learn more about a health condition? With over 2,000 interviews with our physicians and specialists, there's a pretty good chance you'll find what you want to know. Check it out at thescoperadio.com.