Dr. James Beck 00:00:00
Hello everyone, and welcome to the Parkinson's Foundation Expert Briefing. I'm Dr. James Beck, the Chief Scientific Officer of the Parkinson's Foundation. It's a pleasure to have you with us today. Today's briefing, the fourth in our series, addresses an often overlooked yet very impactful symptom of Parkinson's disease, and that is apathy. Apathy can profoundly affect the quality of life of those living with Parkinson's, not only making it harder to stay engaged in daily activities, but also harder to manage symptoms effectively. Apathy can be challenging for both the person with PD, as well as for their care partners and loved ones. However, by recognizing apathy as a symptom and learning how to manage it, we can help improve overall well-being.

Our goal for today is to provide you with some practical tools and strategies to better understand and manage apathy. Before we begin today's briefing, I'd like to take a moment to introduce the Parkinson's Foundation. As a nonprofit organization with the widest national reach, the Parkinson's Foundation is dedicated to improving the lives of those living with Parkinson's by enhancing care and advancing research. Our efforts are deeply rooted in collaboration with the Parkinson's community, ensuring that everything we do aligns with your needs and your priorities. Today's program is another example of how we're working together to meet those goals.

Next, let's take this moment to get to know you, our audience for today. To do so, we're going to launch a poll that will appear on your screen. If you're joining us on Facebook Live, you can respond using the comment section. Tell us what best describes your connection to PD. Are you a person with PD? Are you a spouse or partner? Are you a healthcare professional, physician, scientist or nurse? Tell us why you're joining from your perspective. Let us know by clicking on this, and then we'll be able to share that with everyone who's on our call today.

Just give it a few more minutes. We're collecting the data as people are joining at the top of the hour, and we'll be able to share that information with everyone.

Dr. James Beck 00:02:04
All right. Not surprisingly, most people here are living with Parkinson's disease. Welcome, and care partners are here as well. Thank you very much for joining us, and let's move on.

As you know, with all our expert briefings, we're going to be recording these today, and that's not going to be any exception here. We'll also be emailing you a link to the recording and other resources related to today's topic. If you know somebody who missed today's expert briefing, or if you have to step away, that recording will be something that you can have or share with others.

Now I'd like to take a moment and introduce our expert presenter. Dr. Aaron Malina is a neuropsychologist with over 25 years of experience and practices at Northwestern's Lake Forest Hospital. Dr. Malina spent his formative years in the Midwest, completing his undergraduate education at the University of Michigan, a doctorate from the Illinois Institute of Technology, his clinical internship at Jesse Brown VA Center in Chicago and his fellowship at the Rehabilitation Institute of Michigan. Prior to joining Northwestern two years ago, he managed the psychology service at the Shirley Ryan AbilityLab and worked in both private practice and the North Shore University Health System. Throughout his career, Dr. Malina has worked extensively with neurologic patients and has had the privilege of serving the Parkinson's disease community in various settings.

Dr. Malina? Welcome, and thank you for sharing your time with us today.

Dr. Aaron Malina 00:03:26
My pleasure. Let me just share my screen. Everyone able to see that okay?

Dr. James Beck 00:03:34
Yes, it's perfect.

Dr. Aaron Malina 00:03:36
All right, good.

First, thank you for the opportunity. I'm very excited to talk to this group and also on the topic, as Dr. Beck referenced. This is something that we often don't think about with Parkinson's disease, but we know a lot of patients experience. Hopefully I can share some knowledge to help all of us understand this a little bit better.

Just give me one second. My computer's being wonky. There we go.

First off, I have nothing to disclose in terms of conflicts for this talk.

Our goals for today are to understand some of the clinical features of apathy, specifically in Parkinson's disease. We'll talk a little bit about the differences between apathy and depression, which can both overlap and have some unique features. I'm also going to talk a little bit about anxiety, as well as some of the cognitive or thinking changes that we can see in Parkinson's and how all of those things relate.

We'll learn how apathy impacts both Parkinson's symptom management, as well as relationships and overall lives, and talk about some tools that are available to help us understand apathy, both in terms of assessing or evaluating for the symptom or syndrome, as well as some things that we can do.

I have a few caveats. My friends often note that I tend to speak very quickly, and that's especially true when I get excited about something. I am excited about this topic, so if I start to go too fast, please let us know through the Q&A feature. They can message me and I'll slow down. I'll try to slow down.

I know I have a mixed audience, primarily of patients with Parkinson's or family members, as well as some healthcare professionals. I'm going to be using a number of clinical terms during my talk today, and it's intentional. I want patients to be familiar with and understand some of the clinical terms that you're going to hear your physicians or other providers use. I will do my best to define everything so it makes sense. When you see the screens, some of the terms that are going to pop up are going to be kind of huge, crazy words. I will certainly try to define everything.

Also, as everyone can tell from the gray hair, I've been doing this for a long time. Certainly, for the first part of my career, all the talks I gave were face-to-face. I love that because I'm able to engage with the audience and I can see people's facial expressions, so I get a sense if they're understanding what I'm saying or if things don't make sense.

Obviously, Zoom allows us a much broader audience, but I don't get that direct feedback. If I am talking about something and it doesn't make sense or it's confusing, again, please mention it in the Q&A and our hosts can let me know that, and I can try to clarify things.

Dr. Aaron Malina 00:06:50
Some of this is going to be familiar to many of us, but what is Parkinson's disease? What causes it? It's a degenerative disorder that affects a specific area of the brain called the basal ganglia or substantia nigra, which is here deep in the middle of the brain. The other thing I want to highlight is that it is not just the substantia nigra or those deep brain centers that are getting impacted. The brain is very networked. It has a lot of communications to it, or linkages to it, I should say. Those linkages or networks are also impacted by Parkinson's disease.

The reason I'm highlighting that is that it really does play a significant role as we talk about apathy, as well as mood changes and some of the cognitive changes. Specifically, what happens at the start of the disease is that in the substantia nigra, midbrain, deep in the middle of the brain, there's a loss of cells that produce dopamine, and that plays a role in motor movement, which is why we start to see some of those initial symptoms. But again, it's not just damage to the substantia nigra that causes the symptom profile that we see with Parkinson's disease.

It's damage to the brain's network communications that causes those symptoms, and as we understand that, it helps us understand why some of these changes occur.

I also have to say I have a little bit of a cold, so I apologize if I'm sounding a little bit nasal.

In Parkinson's disease, there is a breakdown in the substantia nigra and a decrease in dopamine in our system. That's something we're all familiar with. The medications we take for Parkinson's disease help to replace that. But there are other brain systems that are also impacted. There's an area deep in the brain, not too far from the substantia nigra, called the locus coeruleus, and another chemical there called noradrenaline is produced. That plays a role in motor functioning. But there are some other chemical systems that can also be affected in Parkinson's disease.

One is the serotonin system, and that plays a prominent role in our emotions. Another is the acetylcholine system, which plays a large role throughout the body, but one of the things it's responsible for is our thinking abilities. As we're going through the talk, you'll see I'll make reference to the fact that we're not just talking about the motor symptoms when we're talking about PD. It's broader.

Dr. Aaron Malina 00:09:22
Back when I started to practice when I was in graduate school in the early '90s, at that point we primarily conceptualized, or thought of, Parkinson's disease as a motor illness. It was the tremor, the rigidity, the slowed movement, what we refer to as bradykinesia, or kind of that hunched posture that Parkinson's patients can sometimes develop because they don't have control of their postural reflexes. Their core is not doing what it needs to do to keep them straight.

But we now appreciate that Parkinson's is a much broader disorder and has a number of non-motor symptoms that can have an equal impact on both patients and families. It's really important that we understand both the motor and non-motor symptoms and implications in PD, or Parkinson's.

We can certainly see what we refer to as neuropsychiatric symptoms. What that basically means are psychiatric-like symptoms due to a neurologic disorder. So it's not that it's a psychiatric disorder; it's a psychiatric sequelae, or consequence, of the Parkinson's disease.

In some patients, we can see hallucinations, where they'll see or hear things that others don't. It's primarily visual hallucinations, seeing things that others don't see.

There can be some changes in impulse control, and sometimes that's due to the Parkinson's. Sometimes it's due to some of our medications, so we may see the person engaging in higher-risk behaviors like gambling. Then apathy, obviously, is a prominent part of our talk today. I'll go into more detail on that in a little bit. But it can also cause changes in our autonomic nervous system, which controls some of our more basic functions like our blood pressure, our breathing and our heart rate. Again, early in my career, we really didn't talk very much about the cognitive or thinking changes associated with Parkinson's disease because it was a motor disorder.

We know that's not the case now, and that cognitive changes are actually fairly common in a lot of Parkinson's patients.

Talking a little bit more about the non-motor symptoms, they are quite common. They're quite prevalent, and that includes apathy, as well as depression and anxiety, which I'll go into a little bit more in a few more minutes. The neuropsychiatric symptoms are sometimes the most bothersome for patients and can have some of the most significant impacts in terms of their functioning, in some patients even more so than the primary motor symptoms. We can see some of these non-motor symptoms early on in the disease, and in some cases we can see them even before the motor symptoms start to present.

I want to highlight that. In some patients, we may see mood changes or cognitive changes before we start to see some of the common initial motor symptoms, such as a tremor.

Dr. Aaron Malina 00:12:21
What is apathy? Apathy is a disorder of motivation, your get-up-and-go, to use a well-worn cliche. It can either be thought of as a symptom or a syndrome all unto itself. It is by no means unique to Parkinson's disease. It's common in Parkinson's disease, but we're going to see it in other disorders as well, including some of the psychiatric disorders, such as depression. We can also see it in some of the other degenerative disorders or dementias, like Alzheimer's disease or something called frontotemporal dementia or Lewy body disease.

Although apathy is quite prevalent in Parkinson's disease and quite common, it is by no means unique to it.

I will definitely dive into apathy in some detail, but I do want to talk about depression, anxiety and cognitive change a little bit first because they're all very interrelated.

When I'm doing a talk with a live audience, I usually ask everybody, who in this room has ever been sad? I know that sounds like a silly question, and I usually get a chuckle, but I do that because everyone raises their hand. Everyone experiences sadness at some point in their life. It's part of the normal human experience. It's expected. It's normal.

Although depression includes sadness, it's broader. Obviously, depression is a mental health disorder, but not only can it cause sadness or irritability, it can affect our thinking, how we perceive ourselves or others, our behavior and our health. Depression does not require a sad or traumatic event to occur for a person to become depressed. It can occur even without that. Depression is fairly common in Parkinson's patients. Depending on the study, we'll see it's somewhere between about 13 and 25%.

This is a very busy slide, and I apologize for that. The reason I wanted to share this with you is that the diagnostic criteria we use is something called the Diagnostic and Statistical Manual. It's now in its fifth edition. These are the criteria for what we refer to as a major depressive disorder, what most people think about as a clinical depression. The reason I wanted to put this up is so people appreciate it's not just depressed mood. That is the first criteria. Obviously, it's very prominent. But we're also going to see decreased interest or pleasure, which could be some apathy; changes in weight or appetite; increase or decrease in sleep; physical slowing; fatigue; changes in thinking; changes in the person's perception of themselves, so they may not see themselves as having the same value or worth; and in the extreme, thoughts that life may not be worth living or suicide.

When I'm talking about depression, this is the depression I'm talking about. It's not just feeling sad, which, again, we all experience.

Dr. Aaron Malina 00:15:23
When do we screen for depression? For every patient that I see, we screen for depression. Certainly, if a person is experiencing any of the symptoms I just described, a red flag should go up. If you think about it, for quite a number of years now, whenever you go to your primary care physician's office for your physical, they ask you those two questions about your mood. We're always screening for depression as part of a physical exam.

I would hope that most of the providers who are working with Parkinson's patients are also asking you the same questions because this is certainly something that we want to be checking in on.

Now let's talk about anxiety in Parkinson's disease. This occurs in about a third of Parkinson's patients, in some studies more commonly than depression. We tend to see a greater degree of anxiety in Parkinson's patients than we do even in other medical conditions. Again, very common.

This is the DSM criteria for generalized anxiety disorder, again, what people think about as clinical anxiety and, again, broader than just being, "I'm nervous." The person's going to have anxiety or worry, typically above and beyond what would be expected for the circumstance. If you have a lion chasing after you, you should have panic. But if you're sitting around and you're worried about a talk you have to give in a year and you're having panic about that, that's excessive. We're also going to see edginess, restlessness, fatigue and changes in thinking. You can see other mood changes like sadness or irritability. We can see muscle tightness, which is very common in anxiety, and it can also impact sleep.

In the same way that depression is much broader than sadness, a clinical anxiety disorder, such as generalized anxiety, is broader than just feeling worried or nervous.

One of the more common anxiety disorders that we'll see in a Parkinson's population is something called social phobia. We used to call this social anxiety disorder. It's exactly what it sounds like. It's being uncomfortable in a social situation, often because of how you think people are perceiving you. They're judging you. They're thinking of you negatively. It can cause people to experience significant fear and often escape from those situations.

We wear our Parkinson's disease on our sleeve. Others can see it, and depending on how we perceive what others are seeing about us, it may make us uncomfortable, and we may pull back from social situations.

Dr. Aaron Malina 00:18:06
Anxiety is often not recognized by medical providers, and this is not their fault. As you know, all providers are seeing a large number of patients. The sessions or the appointments have gotten a lot shorter in time, and we're often focused on the motor symptoms. Sometimes we don't even think about these symptoms, but we know that anxiety and certainly depression can have a negative impact on both the patient, as well as their support network. Something that we often think about is that Parkinson's disease is by no means just a disease of the patient. It very much impacts everybody in their world, be that family, significant others, friends or whatever the case may be.

Anxiety tends to worsen during off periods when the medication isn't working and symptoms become more prominent. As we'll talk about a little bit more, depression and apathy have a fair amount of overlap, less so with anxiety.

I was saying earlier that you don't have to have a depressing event or a traumatic event to experience depression or anxiety. Part of it could certainly be genetics. They can run in families. But when we're thinking about these emotional disorders specifically in Parkinson's disease, you want to think about both biological and psychological contributors. If a person experiences a loss or if a person experiences a trauma, yes, that can certainly impact how the brain is going to process that. But as I was mentioning at the start of the talk, there are lots of networks in the brain.

Some of the networks are the mesial limbic dopamine pathway. The limbic system is the emotional system of the brain. Mesial is a fancy word for in the middle. It's connected to the amygdala, where emotions are processed. Those same changes that can cause your motor symptoms, because of how the brain is networked or internally connected, can also contribute to mood symptoms. As I said earlier, we will have patients where anxiety, or even sometimes depression, will be the initial symptom, and then over time, the Parkinson's motor symptoms will present.

As I said, mood symptoms can have a significant impact on everyone's life. Putting Parkinson's disease aside, anyone who's depressed, anxious or has any other kind of emotional disorder, it affects you.

Dr. Aaron Malina 00:20:15
Now we bring it back to Parkinson's disease, and it affects the patient. It affects everyone around their world. As I was mentioning in terms of the symptoms—I'm sorry, my lights just turned off. Give me one second. There. Sorry about that. They timed off.

Depression and anxiety can also affect our thinking abilities and our physical functioning. In some ways, they can exacerbate some of the changes that we'll see primarily due to the Parkinson's disease. I'll go into this last point a little bit more in a couple slides, but unlike apathy, key components of depression are sadness and what we refer to as negative thoughts, getting down on yourself or getting down on others. We don't tend to see that as much in apathy, but I'll go into more detail on that in a few slides.

Who's at greater risk for depression in Parkinson's disease? Typically those with greater motor symptoms. We're going to see it more in women than men. That's true for the general population. We're going to see it later in the disease as it advances, especially when there's greater cognitive or thinking changes. There are certain genetic subtypes of Parkinson's that are also more prone to depression.

Contrary to that, anxiety tends to occur earlier on. Well, let me take that back.

Dr. Aaron Malina 00:21:42
When folks develop Parkinson's disease earlier on in life, that's where we tend to see more anxiety. When there is a fluctuation in symptoms and you don't know when you're going to exhibit X, Y or Z, you become worried about it. It makes sense. Again, we know that all mood disorders, be it anxiety, depression or really anything else associated with Parkinson's disease, are going to contribute to a lower quality of life for everybody, the patient and everyone around them. It's really very important that we are actively monitoring and treating this.

How do we diagnose mood disorders? Again, patients oftentimes don't talk about it. They can be reluctant to acknowledge it. Sometimes there are stigmas against emotional disorders, especially within certain cultures.

We tend to hear more about these concerns from the support network, the spouse, the partner, whatever the case may be. As I was going over the symptoms of depression and anxiety, as you saw, a lot of them can overlap with what we typically think is due to Parkinson's disease. Providers, or even family of the patient, may make assumptions that they're experiencing things because of the PD and less so because of emotional disorders. Again, time-limited appointments, trying to make sure we get the motor symptoms under control, questions may not always get asked about mood, although we certainly have a greater awareness of it now, and providers have gotten much, much better about checking in on folks to see how they're doing in terms of their emotional well-being.

How do we treat anxiety and depression? There are two main pushes. First is medication: antidepressants, medications for anxiety. You'll hear classes of medications like the SSRIs or SNRIs. These are medications that impact some of those neurotransmitter systems in the brain.

Cognitive behavioral psychotherapy is a shorter-term, educationally based talk therapy where the person learns to understand how their mood symptoms are impacting both how they're thinking and how they're feeling, and then giving them some tools to address those symptoms so they feel better. Exercise, staying active, is an extremely important part of treatment for both Parkinson's disease and mood disorders. I gave a talk a little while back for one of the local Parkinson's groups, and they had a phenomenal exercise group come out and everybody was kind of moving and shaking. It was a lot of fun to watch.

Afterwards, I asked folks, anybody feeling different now than they did before that session? It was pretty consistent that folks were feeling better because they got up and moving. It's good for Parkinson's disease. It's good for your mood. As we know, it's really kind of good for everything.

That's a little bit about depression and anxiety. Now let's focus on apathy.

Dr. Aaron Malina 00:24:42
The key feature, or the key defining feature, of apathy is decreased motivation. That's not due to a person not being conscious. It's not due to a person having thinking difficulties, and it's not directly due to a person having emotional distress. This next statement is a little more scientific: it's an absence of a response to a stimulus. Something happens, and the person doesn't respond to it the way you expect them to. It is not just a reaction to disability. Just because a person has Parkinson's disease or another neurologic disorder, it's not just an emotional reaction. It is a neurobiological change, although psychosocial factors, things that are going on in your world, can impact it. The take-home here for everyone is that apathy is a disorder of motivation. You just don't have the drive you did in the past to do things or to engage in things.

In more common terms, what is apathy? It's less interest in doing things. It's putting less effort forth even when you do things. Getting started is the hardest part, taking that first step, initiating activity or beginning to do something. Over time, we'll see a withdrawal where the person steps back away from their normal activities, their normal social circle, even in some instances, close family or friends. They seem disinterested. They don't really seem to care. They're not bothered by it. We'll often see a lack of emotional expression.

That can sometimes be confusing in Parkinson's disease because, as we all know, one of the main symptoms of Parkinson's disease is a lack of facial expression. Think of this as kind of an add-on to this. Basically, the person is not responding to what's going on in terms of their world around them, what other people are saying, what other people are doing, what other people may be feeling and expressing. There's just a lack of connection there.

There's a triad of symptoms that we think about with apathy. Again, this is not unique to Parkinson's disease. It's true for other neurodegenerative and psychiatric disorders. The big three are the behavioral, cognitive and emotional symptoms of apathy, and then I'll include social as a fourth, which you'll see in some studies.

The behavioral syndrome or symptom is something called the auto-activation deficit. That is the connection between the basal ganglia, that part of the brain deep in the middle, and the frontal lobe, the front part of the brain, with network connections. What we'll see there is a person who is lacking in initiative and has what we refer to as cognitive inertia. They're just not getting up and doing things. They become less productive and often more dependent on others.

Cognitive symptoms, or thinking symptoms, again, are primarily in the frontal lobes of the brain, a little bit of a different part than we'll see with the behavioral symptom, but it's again due to connections between the basal ganglia, deep in the middle of the brain, and some of the networks leading up front.

The person is going to have decreased interest in novelty and new things. They don't want to engage, and you'll see less of an interest in planning, organizing, kind of doing everything we need to do so that we can participate in activities. They let that fall by the wayside. They let others take over. Sometimes they then participate, sometimes not.

The emotional symptoms are what we'll sometimes refer to as the reward deficiency syndrome. Again, it's due to the connections from the basal ganglia to the frontal lobe, lower part of the brain. Now, something called the orbitomedial prefrontal cortex is the green area down here. You'll see a blunted affect, a lack of response to both positive and negative events, less concern for what's going on in the patient's world, less awareness of or concern for what's going on in others' world, and just a general indifference. The fourth part of the triad is social engagement. This is something we're studying more about now, but it's not just a lack of interest in participating in activity.

Dr. Aaron Malina 00:28:43
It's a lack of interest in participating in relationships, and that very much impacts both the patient's caregiver, significant other, as well as their entire network.

Apathy is very common. Depending on the study, anywhere between about 16% to about half of patients. We can see it in both what we refer to as primary Parkinson's disease or parkinsonism. Real quick, Parkinson's disease is when there is a breakdown in the dopamine-producing cells in the substantia nigra, causing the symptoms that we're all familiar with. Parkinsonism is when similar areas of the brain are damaged by other processes but cause kind of a similar presentation.

Apathy is very common. It's one of the major neuropsychiatric features, and I know this is a complicated diagram I have up here, but this is really showing some of the networking between the basal ganglia of the brain and some of the frontal lobe areas.

The way you want to think about it is the primary issue is with incentive processing. A person has something where you would expect them to respond, and they're unable to do so. They're unable to process that there's something that has greater value or valence. They can't differentiate if it's a favorable, good or bad outcome, and then they don't know how to respond to that. If you think about it, when you have something good happen in your world, you react to it emotionally, and then you may have a behavioral response to it. That whole system is breaking down for folks with apathy, especially in Parkinson's disease. They don't identify something as having either good or bad value.

It doesn't necessarily trigger the emotion, and then we don't see any kind of behavioral or physical response.

Apathy can really have a big impact across the spectrum for patients. We can sometimes see a poor response to treatment for motor symptoms. Sometimes it's even hard to get patients into the doctor to see the doctor or to take their medications. They struggle with day-to-day decisions.

It can sometimes lead to increased healthcare costs because we'll see a drop-off in compliance. People stop taking their medications or doing the things they need to. Again, we can think about apathy as kind of being an independent thing caused by dysfunction in brain circuits. Sometimes it happens on its own. Sometimes it's due to any other number of neurologic or different psychiatric disorders. It falls on a continuum. Reduced motivated behaviors is someone who just doesn't want to get up and do anything. The most severe presentation is something called akinetic mutism, where the person doesn't talk, or abulia, an absolute absence of willpower. Drive is totally gone.

Like Parkinson's disease, where there can be milder symptoms, more moderate symptoms or severe symptoms, the same is true for apathy. There may be a mild drop-off in motivation, or we could see a more significant or severe presentation.

We're not 100% sure why it happens, but again, it really is dysfunction in the basal ganglia, deep in the middle of the brain, the substantia nigra where that dopamine is created, and the connections or links to the frontal lobes of the brain, the part of your brain right behind your forehead. It's not something that you're going to see on a structural scan like an MRI or a CT. It's not like those parts of the brain shrink. Parts of the brain are still there, but the network connections are what get impeded and can contribute to apathy occurring.

Dr. Aaron Malina 00:32:24
These are some of the areas of the brain. Prefrontal cortex, again, is the part right behind the forehead, and processes emotional information. They process drive, and they process our motor movements and behavior. All of these things are interlinked that keep a person with Parkinson's with apathy from reacting. It's a disruption in those connections. We can also see not only less dopamine being produced, but there may also be less absorption of it in the brain. The brain produces it; other parts of the brain absorb it.

It can fall apart in either part there or in the connection, and we can see apathy starting to form. Where we more commonly see apathy in Parkinson's patients is with folks who are older.

Folks who have less educational attainment tend to show a little bit more of this, and this is likely one of the psychosocial contributors. Sometimes folks may have a little bit of what we refer to as health literacy, a little less awareness of why things are occurring and how things are occurring, so they have a greater expression of symptoms. We can certainly see it with depression. We can see it with cognitive impairments. We can see it as the disease goes on for a longer period of time, and for patients who have a REM sleep behavior disorder. The folks who are moving a lot, acting out their dreams or flailing in their sleep, talking in their sleep, can often have apathy associated with that as well in the context of Parkinson's disease.

With depression, coming back to a primary depression, it's kind of the lower part of the frontal lobes, the front part of the brain, where we're going to see more depression. Apathy is going to occur a little bit higher up and a little bit more toward the middle.

It is related to a breakdown in the brain's reward circuitry around responding to our environments, but it's also going to impact other symptoms. As I was saying, our acetylcholine system, our serotonergic system, emotional system, so both our thinking and mood symptoms. You want to think about apathy and depression as being unique constructs, but they also overlap. Apathy can occur with or without depression. It's really very important that we try to screen for both apathy and depression with patients so we can try to figure out where it's coming from and address it better.

There's a lot of overlap. With apathy, as I've gone through, there is decreased initiative and decreased drive. With depression, there is sadness, guilt, negative thoughts, and at the extreme, suicidality. But there's also a lot of overlap. We're going to see psychomotor retardation, which means the person is moving slowly.

Anhedonia is an inability to experience joy. Energy is going to be down, less physical, decreased enthusiasm. These symptoms can be either. When a person is presenting with this list of symptoms they have up on the screen now, you want to be thinking toward, what could it be? Could it be apathy? Could it be depression? Could it be both? You want to get it assessed so we can get it treated.

Dr. Aaron Malina 00:35:21
I want to talk quickly about cognition or thinking ability in Parkinson's disease.

Again, early in my career we didn't really talk a lot about thinking difficulty in Parkinson's. Now it's recognized as a very common non-motor symptom. Initially, it's due to a breakdown in that same dopamine system causing some of the motor changes, and then over time other chemical systems in the brain become impacted and we can see broader changes in a person's thinking.

Not all patients will have global changes in their thinking from Parkinson's disease. Most patients experience what we refer to as some executive dysfunction, higher-order thinking abilities, which I'll talk about in a slide or two. But we know that in the same way that apathy is associated with a lot of changes, so is cognition or thinking abilities. It can negatively impact a person's quality of life. It can increase their risk of not being able to be in their home. It can be expensive in terms of healthcare costs and has a significant impact on the people that love and take care of patients with Parkinson's disease.

The initial change in terms of thinking ability, as I was saying, is executive functioning. That's a person's ability to problem solve, reason, organize, plan, manage. If we see apathy in a patient, it can be a predictor that we may start to see more cognitive changes. Again, that's something we want to monitor for.

This is kind of a horrible drawing I put together, but this is a little bit about how the thinking process works in general, and I'll use that to explain what's happening in Parkinson's disease. This big box over here is your memory, and the little small boxes under new info are things you want to learn.

Under normal circumstances, the brain puts information into memory by organizing it or associating it, and that helps to get it into our short-term memory. You want to think about your short-term memory as basically being a holding tank: small, doesn't last very long. If the information is important, we transition it to our long-term memory, much bigger, lasts a lot longer. Then when we need the information, we go into our long-term memory and pull it out.

But for the information to get into our memory first, it has to go through a couple of filters. The first one is we have to pay attention to it. We have to focus on it. If we focus on it, then we have the potential to learn it.

The next one is we have to understand it. If we don't understand what's going on, we may learn something, but what we're going to learn may be incorrect.

In Parkinson's disease, the major changes that we see are in a person's retrieval, their ability to pull information out of memory, and in their attention. Slowed processing, the gears of the brain turning slower, is a common cognitive symptom in Parkinson's disease. People can miss stuff, if you will, at the front end where they're not able to pay attention to it, or they may have difficulty pulling it out of memory. These thinking abilities are what we refer to as executive thinking abilities. Again, if you think about apathy and some of the behavioral changes we'll see with Parkinson's disease, the cognitive changes are related.

Dr. Aaron Malina 00:38:32
Again, we're going to see greater apathy in patients with more cognitive impairments. It's not uncommon to see what we refer to as executive dysfunction earlier on, problem-solving, reasoning. We're going to see more general changes in terms of slowing and memory retrieval as the disease progresses in some patients. It's not by any means everyone.

Apathy can be present early on in PD and can also occur later, depending on what's going on with the patients. It can occur even without what we refer to as more generalized cognitive deterioration or real breakdown in the person's thinking, but it's often associated with that executive dysfunction, that higher-order thinking ability.

Both depression and apathy come from the connection between the motor system of the brain and the emotional systems. That's the dopaminergic mesocorticolimbic system. Motor, mood: much easier to remember. You want to think about apathy as being kind of a specific affective or emotional system, but it's different. It's more motivationally driven.

There's a huge association, again, between apathy and executive functioning. We're also going to see a relationship between apathy and cognition. Apathy has a huge impact on both the patient and everyone around them, including the medical providers, family and friends. I know many of us are very familiar with this.

How do we look for it? It's really going to be important, and providers are certainly getting a greater understanding that we screen for depression and apathy in Parkinson's disease. We want to know if it's there. We want families and patients to understand it. We want to treat it. If we're aware of it and asking about it, we can do something about it. That's really the important goal.

There are some specific questionnaires. You may see something called the Lille Apathy Scale or the Apathy Evaluation Scale. These are questionnaires your provider may have you fill out, specifically looking at apathy questions.

This is the scale that neurologists are using to gauge the severity of your Parkinson's disease, and there are specific items on here that they're going to be asking you about to look at apathy. We really try to capture it either with questionnaires we're going to have you fill out or with observations and conversations that you're going to have with your provider.

Once we identify that a person has apathy, what do we do? Some folks may be familiar with a deep brain stimulator. It's a device that can be put into your brain to help with controlling motor symptoms. It can sometimes also have an impact on apathy.

TMS is magnetic stimulation to the brain. There are a lot of non-medication treatments, so exercise and activity play a huge role, engaging in your world, and then some of the cognitive therapies can be very effective. Depending on what kind of apathy you're showing, there are different medications that may be available if it's more related to lack of drive in terms of your thinking, your behavior or lack of emotional expression. The better the understanding your provider has of what you're experiencing, they can be a little bit more targeted in terms of the therapies or medications they may use for you.

There are some references that are available where this all came from. Thank you very much for the opportunity.

Dr. James Beck 00:41:58
There we go. Excellent.

Thank you, Dr. Malina. That was really a lot of information, and I appreciate you sharing that with us, reviewing all these details about apathy. Before we jump to the questions I'd like to ask of you, I just want to again encourage all our viewers, our audience, to put questions into the chat as they have them. We'll do our best to answer them as we go through there. Unfortunately, time is limited, and if you're joining us via Facebook, go ahead and put it into the comments. My colleagues on the back end are sorting these together and feeding them to me so that I can then share with Dr. Malina as part of the process. As always, if we can't get to your questions, we do have a wonderful resource through our Helpline that will be able to help as part of that process.

Again, thank you for this overview, Dr. Malina. Let's get to what Brad, one of our viewers, said is, in a nutshell, to describe apathy: apathy with PD is caused by real changes in the brain, and it's not just a PD patient's perspective or reaction to the symptoms. This is something that is organic as part of the process. Is that correct?

Dr. Aaron Malina 00:43:03
Yes and no, but it's both. There are absolutely physical changes that are occurring in the brain, but we are also reacting to our environment, and then those physical changes in our brain react to the environment. You want to think about it as both a physical change and then potentially a response to what's going on around you.

Dr. James Beck 00:43:20
Excellent.

When people are experiencing apathy, several questions have come in. One of the basic ones is, does someone know they have apathy? How does someone have that insight to understand that they have it? Is it going to really rely upon their family members? One of our viewers says Jennifer has this and she doesn't know how to address it with her mom.

Dr. Aaron Malina 00:43:40
It's a wonderful question. Oftentimes earlier on in the disease process, a person will show greater awareness of the apathy. As the disease progresses, certainly as the apathy progresses and their lack of motivation worsens, they're monitoring themselves less, then we're going to see a drop-off in it. If you're seeing it in a family member, if any of the symptoms I described, either potentially due to depression or apathy, may be present, have a conversation with the person in your life and let them know, 'I'm seeing that you're less motivated about things. You're seeming less down about things. Let's talk to your doctor about this next time we're there. Maybe there's something we can do about it.'

Dr. James Beck 00:44:26
Fantastic. Do you find that when you take that approach, are people apathetic in their response? Does it require convincing as part of this process, or do you think that they'll be like, no, no, I'm fine? Again, as you pointed out, there are all these other aspects they don't necessarily want to engage in or think about. You make it sound very simple, but I imagine it's a little bit more complex.

Dr. Aaron Malina 00:44:45
Oh, absolutely. No, I was definitely oversimplifying it. It's going to vary.

Dr. Aaron Malina 00:44:57
Some people are going to be more aware of it, more willing to engage. Some people less so. Part of it is also going to depend on what the person's personality was like before. If you have a family member that's always been stubborn and unwilling to deal with anything, this isn't going to help.

It's not going to make things better. It's going to make it worse. If you get some pushback, that's understandable. It's actually quite normal. You want to have those conversations every now and again, in casual terms, when it's a good time, continuing to seed the idea. Then over time, hopefully you can talk about it with the doctor, present it to the healthcare provider. But no, it's not easy. You're going to get pushback. In the same way that, for a lot of patients, when we had that initial tremor or other motor presentation, the person was dismissing it, dismissing it, but you stayed with it and you eventually got them to see the doctor, this is really no different.

Dr. James Beck 00:45:47
Okay. All right, well, that's good to know as part of that process. Another question comes to mind. You touched on it a little bit at the beginning when we were looking at the different symptoms for major depressive disorder, and fatigue is one of them. Fatigue is a real issue for people with Parkinson's as well. How do you differentiate someone experiencing apathy versus fatigue? Maybe there could be overlapping as well, as we see with depression and apathy, that it's not exactly each one is a silo to itself.

Dr. Aaron Malina 00:46:23
They are by no means silos. They can occur separately, but they very often do co-occur and are very much intermingled.

You can certainly see fatigue in depression, but if it's just fatigue and none of the other symptoms like sadness, changes in sleep, appetite or interest towards the future, it's less likely depression. You can certainly see fatigue in apathy. But again, if it's just fatigue but the person's motivation is good, they're just tired, then perhaps we're looking at something different, or it's going to be some combination thereof. It's really hard to parcel these things apart. What we try to get an appreciation for is, is the person depressed? Is the person anxious? Is the person tired or fatigued?

If it's all three, we're going to treat all three. We're going to do things to address all three. Sometimes we can tease them apart. Sometimes we can't. It's more important that we identify that it's there, whatever it is, be it fatigue or another symptom, and bring it to our medical provider's attention so that we can get some help for it. Sometimes we're able to clarify it's due to one thing. Sometimes we're not, but regardless, we're able to address it.

Dr. James Beck 00:47:35
Fantastic. When we talk about addressing it, can you go over a little bit more detail, like medications that might be available? You mentioned DBS as a potential therapy.

When it comes to these antidepressant medications, do you find that they can be employed as well to tackle this, or can you elaborate? Yeah, if you wouldn't mind elaborating a bit more on that.

Dr. Aaron Malina 00:48:00
It depends on the person's presentation. Do they have both depression and apathy? Is it just apathy? But there are certainly antidepressants that we can use for a person that's showing more of an apathetic presentation. There are certain antidepressants that are more stimulating. They kind of give the brain a little spank, if you will, to get the person up and moving. There are stimulant medications that we can sometimes use. Some of those are the things you think about for ADHD, like Adderall or Ritalin. Those can sometimes be helpful. Structure and behavioral activation are especially important.

Yes, there are medications that we can use, but structuring the person's environment, building in ways for them to get up and moving, is an essential, essential part of treating it.

Dr. James Beck 00:48:46
Is that what you mean by behavioral activation, that structure in order, a plan with which to activate someone behaviorally as part of that process?

Dr. Aaron Malina 00:48:56
Correct.

It's literally laying it out into components. If you have a person that's on the couch and won't get up and move to shower, you're not just going to say, okay, let's go get up and shower. They're not going to do that. But if you can lay out to them, okay, right now we are going to stand up. You get them up, if they're able to, and talk to them for a second. Now we're going to do this. Now we're going to do that. Then as you build things over time, you're also checking in with the person: okay, now we're up and moving a little bit. How are you feeling? Hopefully the person is feeling a little bit better, and that's reinforcing. Yeah, it's helping to build a scaffold around the person, providing them with the steps and then some reinforcement to encourage those behaviors along.

Dr. James Beck 00:49:37
I often hear expressions about terms like self-efficacy. Is this kind of, in essence, what we're talking about? Particularly, I hear about self-efficacy around exercise and trying to remove barriers for people so that they can go out and become physically active. Is a similar approach being utilized here in trying to...

Dr. Aaron Malina 00:49:56
Yeah, I would say that too.

When we're talking about self-efficacy, how do you feel about yourself? How do you perceive yourself? Part of the apathy is a lack of drive. It's an internal lack of that push to get up and do things. Certainly, if you're not feeling very good about yourself, it can worsen it. The apathy can occur even if the person is feeling okay about themselves. But yeah, the treatment is very similar. You're not feeling very good about yourself because you're not doing whatever it is you need to be doing. If we can get you up, if we can get you moving, if we can get you involved, you'll feel better, and oftentimes you'll feel better about yourself. They're related constructs.

Dr. James Beck 00:50:33
Okay. That's awesome. The Foundation has a big undertaking around genetic forms of Parkinson's disease, and we're aware that a small number of individuals, maybe 10 to 15%, have the genetic types of Parkinson's disease. Have you seen a correlation with any of these with apathy? Perhaps people might have a LRRK2 mutation or a GBA mutation, or is that still to be determined?

Dr. Aaron Malina 00:51:00
Yes and no. We're still obviously learning about the genetic contributors to it, but in some of the more genetically loaded Parkinson's disease subtypes, we can see greater apathy. It's still early on in terms of our understanding.

Dr. James Beck 00:51:14
Okay. Fantastic. As care partners who are seeing their loved one who is apathetic like this, you mentioned right now an approach of how to get them up to get showered. Is that what it really comes down to, just breaking down tasks into individual ways to help them go visit the doctor to address their apathy, get up and out of the house, maybe go walk around the block or engage in social situations? What other means can a care partner do in order to really help with them?

In essence, instead of necessarily trying to go, quote-unquote, fix their loved one, how are they able to manage engaging with their loved one in this situation? Because not everyone wants to be fixed, I guess.

Dr. Aaron Malina 00:52:11
That's a great question. Part of it is certainly that assessment piece. Why is the person not getting up? Are they apathetic? Are they physically ill? Are they depressed?

Are they anxious? Are there other things going on? Are there stressors around them? As much as you're able to engage in a conversation with a person: what's going on here? Do you not want to go and do this because you're feeling sad? Is it hard for you to do it physically? Are you worried something is going to happen? Or do you just not have that get-up-and-go?

Depending on what's contributing, that's where we try to guide things. If you have a sense that your family member may be a little bit more depressed, then it's a conversation with the medical provider about medication, maybe having the patient see a psychologist to talk through, to engage in some of the talk therapies we can do for depression. Then as part of that, you build in that behavioral activation or structuring. Yes, part of the treatment for apathy is helping the person to structure their world, but it's really important that you think about it more broadly.

Parkinson's disease, to state the obvious, is a very complex disorder, and if we can really understand where the behavior is coming from, then we can address it properly. If a person's majorly depressed and we're just trying to get them up and going, yeah, it'll help. But if we're treating the depression more directly with medication and therapy while also getting them up and going, we're going to have greater success.

Dr. James Beck 00:53:35
Got it.

When we talk about success, what kind of rates are we talking about here? As we tackle apathy from various angles, is this something we will see eliminated, or is it something that now becomes controlled, if you will? Like they will always have apathy and it is just something that they're able to manage better along with other aspects of their disease.

Dr. Aaron Malina 00:54:00
I really do wish it's something we could just make go away, in the same way I wish we could make the tremor or some of the other symptoms just go away. I think, as with many of the symptoms associated with Parkinson's disease, we're really talking about management. It's trying to minimize either the severity of the symptoms or their impact. If a person has a depression and it's just a, quote-unquote, simple depression in the context of Parkinson's disease, we may be able to get that to a point where it really isn't as present. But if a person is having some apathetic features, we're largely trying to decrease the severity and minimize the impact.

We may not make it fully go away, but even if we decrease it to a small percentage, it can have a pretty positive impact on both the patients and everyone around them.

Dr. James Beck 00:54:46
Yeah, for certain.

Another question that comes in is trying to understand the intentionality for the person who is apathetic. It seems to me from our discussion that it's almost beyond their control, so they don't want to do things. It's not intentional, like I don't want to because I don't want to, but it's more this psychological milieu that's been imposed upon them, and it's changed their mood and their behavior. I think that would be helpful for care partners who are frustrated.

Dr. Aaron Malina 00:55:19
In the same way that you wouldn't quote-unquote blame a Parkinson's patient for having a tremor or having stooped posture, neurologic symptoms, we understand that as part of the disease.

Apathy is the same way. This is part of the disease. It is not something the person is choosing to do. In the same way, if a person has forgetfulness, it's not that they're choosing to be forgetful.

It's part of the disease process. As you're thinking about it, you don't want to be quote-unquote blaming the patients. We often talk about blaming the disease. It's the disease's fault, if you will, that this is occurring. But again, personality comes into play. If you have someone that was stubborn or pushed back a lot before, yeah, there may be some contributors there as well. But no, apathy can absolutely just be a direct result of Parkinson's disease and is not something the patient is choosing to do.

Dr. James Beck 00:56:15
Yeah, I think that's really helpful because, again, there's that tension that can be there and the frustration of loved ones. You mentioned a tool during your presentation for assessing apathy. I couldn't remember, is that a self-assessment? What's the best, because there were a couple different tools, ones that use the UPDRS or...

Dr. Aaron Malina 00:56:35
It varies.

Sorry.

There are forms that get filled out. Sometimes that's by the patient, sometimes that's by the caregiver, their support person, sometimes it's by both. Sometimes it's dependent on observation of either the medical provider or a caregiver. Depending on what measures are being used, we really want to, as with anything else, if we can get multiple sources of information, it tends to be more reliable and it gives us better information to act on.

Dr. James Beck 00:57:05
Okay. Is there a tool that you would recommend as a self-assessment screening tool that can then lead to a good conversation with someone's clinician? Say I took this assessment, and I appreciate it could be for depression, maybe not something specific for apathy, but what should a person with Parkinson's or their caregivers do to get this conversation going with their clinician?

Dr. Aaron Malina 00:57:31
Sure.

When you go to the doctor and they ask you those couple of questions about depression, that's something called the PHQ-2. There's a PHQ-9. It's a longer version of it, but it's a list of some common depressive symptoms available in the public domain. You can get it off the internet, and you can sit down with the person and talk about, are you experiencing these things? If they are, maybe we should talk to the doctor about it. The Apathy Evaluation Scale is a longer scale, but it's also available. Again, if you go through some of the symptoms, talk to your family member about it, and if it seems like some of those things are occurring, it's trying to have the conversation. But don't feel like you have to go out and get a specific measure.

For some folks, having that objective measure makes the conversation easier. I very much appreciate that. But if you have a familiarity with the different symptoms and you either see the person experiencing it or they're talking about experiencing it, then use that as an opportunity to say, you know, I saw on the internet, or wherever you may have gotten it from, that that could be associated with this, this or this. We can't figure out what that is. Let's talk to your doctor about it.

Dr. James Beck 00:58:34
Okay. That's perfect.

What a wonderful way to end this. I want to thank you, Dr. Malina, for offering your time today for our expert briefing on the challenges of apathy with Parkinson's. They're certainly there. I want to thank everyone who was able to join us today. We had a tremendous response during our Q&A, and unfortunately, we were not able to get to them all. So please, if you still have your question unanswered, call our Helpline, 1-800-4PD-INFO. They're on standby and will be able to address it the best they can. There's still a lot to learn about Parkinson's, and your engagement can support our efforts to learn more about Parkinson's and research and how you can get involved.

Please check out our website at Parkinson.org/Research. Our next expert briefing will be held on October 9, and here we'll be exploring the subject of managing multiple chronic conditions beyond simply Parkinson's disease. You can learn more about our future topics and register at the webpage that's right here on our screen, Parkinson.org/ExpertBriefings, as part of that process. In addition to today's expert briefing, the Parkinson's Foundation also offers a wide range of virtual education and wellness programs each week through our PD Health at Home series.

This includes Mindfulness Mondays, Wellness Wednesdays, Fitness Fridays, and our Spanish language series, EP Salud en Casa. Hopefully I did that well. In the meantime, we're here for you. Please do not hesitate to reach out to us. We have a comprehensive website and many more resources that address everything related to Parkinson's disease at Parkinson.org. You can also call our Helpline, again, that's 1-800-4PD-INFO, or you can email us at Helpline@Parkinson.org.

As we see with many of these webinars, before you go, the screen is going to go black, but we want your input. This is what we use to improve our webinar series from the time it's begun, and we'll continue to do so. Again, it's done in partnership with you. Give us your feedback. We utilize that to make our webinar better. We also share that with our presenter so they can improve their skills or address topics that you felt weren't covered well enough. So please, at that moment, fill out that survey, which will pop up when this window disappears. Until next time, I'm Dr. James Beck at the Parkinson's Foundation.