Apathy and Alzheimer’s Disease: Plenary Preview with Dr. Krista Lanctôt

Dr. Nathaniel Chin: Welcome back to Dementia  Matters' special series covering AAIC 2022, where we’re getting to know the plenary  speakers who will be featured at the conference. To hear more from these speakers  and learn about their research, you can tune into their plenary talks virtually by  registering at aaic.alz.org, or through the link in the episode description. Access to the plenary  sessions is free to the public with registration,

so be sure to register before the event  starts on July 31st. On today’s episode, I’m joined by clinical pharmacologist Dr. Krista  Lanctôt. Dr. Lanctôt is a senior scientist in the Hurvitz Brain Sciences Research Program at  Sunnybrook Health Sciences Centre and a professor at the University of Toronto. Through her 25  years of pharmacology research, Dr. Lanctôt has studied neuropsychiatric symptoms like apathy  and agitation in connection to Alzheimer’s disease

and other neurocognitive disorders. Her AAIC  talk on apathy in neurodegenerative diseases will take place on Monday, August 1st.  Dr. Lanctôt, welcome to Dementia Matters. Dr. Krista Lanctôt: Thank you, Nate.

of symptoms that occur in persons with dementia  – neuropsychiatric symptoms. That term refers to a host of behavioral and mood symptoms that  accompany Alzheimer's, like apathy and agitation. Apathy is the most frequent of these. It's a  big contributor to lower quality of life. The frequency impact and lack of approved treatments  are what drew me to focus on this symptom.

You have an extensive research background  in clinical pharmacology. Can you explain for our listeners the relationship of pharmacology  and symptoms such as apathy and agitation? Lanctôt: In any group of people with  Alzheimer's disease or related dementias, some patients will have apathy or agitation,  but some will not. Why the difference? Ongoing research by my lab and other groups is linking  these symptoms, such as apathy and agitation,

to specific brain chemicals in their brain  receptors and brain circuits. It's an important link because it's that which provides clues as  to which pharmacologic treatments might work. It's amazing to think about our emotions and our symptoms being broken down into the  chemical relationships of our brain cells and the things happening in our brain cells. So it's your  hope to understand that so then we could then use pharmaceuticals or other  interventions to help people?

Lanctôt: Correct, because when these behaviors  are such a change from the way that you've acted for your whole lifetime and they're in  the context of a neurodegenerative disease, we think that it's the neurodegenerative  disease that's contributing to that. That's probably our best  avenue for helping with them. I think it's also helpful  to say to people when they see their loved one experiencing some  of these neuropsychiatric symptoms,

well it’s not that they're trying to do this.  This is a result of changes in the brain and the chemistry changes that are happening  because of neurodegeneration. Is that right? Lanctôt: That's exactly right. It's so  difficult to deal with these behavioral changes and I think it really helps the  care partners of persons with dementia.

When you point that out to them, that  it's not the person doing it on purpose, that there are actually changes in the brain that  are contributing to that, it's no one's fault. And I'd like to get to a definition,  because I think it's important for people to know the difference. How do you define  apathy and why does it develop in brain diseases like Alzheimer's disease  and vascular disease in particular?

Lanctôt: In the context of Alzheimer's disease  and other brain diseases, the term apathy refers to diminished initiative, diminished  interest, and diminished emotional responses. So a person with dementia might lose interest in  hobbies or activities or the people around them and they might stop initiating any activities or  interactions. Importantly, they stop responding to both happy events and sad events so they have  emotional blunting. We think it develops when the

structures that are associated with motivation  are impacted by these brain diseases. My group specifically showed deficits in the brain reward  system. It's also tied to injury in areas that are associated with planning and insight in the brain,  which makes it even more difficult to treat. Some of those symptoms that you're  describing or experiences sound like depression. Is apathy the same thing as depression,  or how would you differentiate the two?

Lanctôt: You're exactly right. A  lot of the symptoms of depression overlap with some of the symptoms of apathy. For  example, lack of interest overlaps. The main thing that distinguishes the two are the feelings of  sadness or the feelings of worthlessness that happen with depression. Apathy is different  because it's complete emotional blunting.

They're not feeling sad. They're not feeling  happy. They're not feeling anything. It's important to distinguish because there are  different treatments for depression and apathy. That's a perfect segue  into my next question for you, which is what can be done for people  experiencing apathy right now? Lanctôt: First, once medical causes  for any behavioral changes like infections are ruled out, the first step in  treatment is always non-drug interventions,

like supporting the person with planning  and initiating. For apathy, sometimes medications like cognitive enhancers donepezil,  rivastigmine, and galantamine help with apathy. Once those have been tried, our recent  results from the ADMET 2 trials suggest that a trial of methylphenidate may  additionally help some people with apathy. What do you think the research landscape on apathy and neuropsychiatric symptoms  will look like in the next five years?

Lanctôt: That's a good question. The field,  in general, is moving to earlier detection of brain diseases like Alzheimer's by using  brain scans and more recently blood tests. Over the next five years, I actually hope these  research tools will start moving to the clinic. For neuropsychiatric symptoms like apathy,  their late-life presentation should prompt the use of these diagnostic tests to allow  early intervention and precise intervention.

Can you provide us with some  key takeaways from your presentation at AAIC? And I don't want you to have to  steal your thunder from the day itself, but if anything our listeners could  hear now before they attend your talk. Lanctôt: For key takeaways, I think it's important  to know that apathy is frequent and it has a negative impact on persons with dementia. There  are recent advances in defining this syndrome

and helping us understand its underlying causes.  The recent ADMET 2 trial of methylphenidate also shows that apathy can respond to medications  and that paves the way for future clinical trials. There is hope that earlier identification  and treatment can maintain quality of life. What topic or talk are you looking  forward to hearing about at AAIC 2022? Lanctôt: I'm really excited to hear the latest results from clinical trials of  novel targets and new biomarkers.

With that, thank you, Dr. Lanctôt, for  joining us on Dementia Matters. I look forward to seeing your plenary talk at AAIC and hope to  have you on for a separate episode in the future. Lanctôt: Thanks so much,  Nate. Nice to speak with you. Outro: Thanks for listening to Dementia Matters. Be sure  to follow us on Apple Podcasts, Spotify, Google Podcasts, or wherever you get your podcasts to  be notified about upcoming episodes. You can also

listen to our show by asking your smart speaker  to play the Dementia Matters podcast. And please rate us on your favorite podcast app -- it helps  other people find our show and lets us know how we are doing. Dementia Matters is brought to you by  the Wisconsin Alzheimer's Disease Research Center.

The Wisconsin Alzheimer's Disease Research  Center combines academic, clinical, and research expertise from the University of Wisconsin School  of Medicine and Public Health and the Geriatric Research Education and Clinical Center of the  William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from  private university, state, and national sources, including a grant from the National Institutes  of Health for Alzheimer's Disease Centers.

This episode of Dementia Matters  was produced by Rebecca Wasieleski and edited by Caoilfhinn Rauwerdink. Our musical  jingle is "Cases to Rest" by Blue Dot Sessions. To learn more about the Wisconsin Alzheimer's Disease  Research Center and Dementia Matters, check out our website at adrc.wisc.edu. You can also follow  our Facebook page at Wisconsin Alzheimer’s Disease Research Center and our Twitter @wisconsinadrc.  If you have any questions or comments, email us

at dementiamatters@medicine.wisc.edu.  Thanks for listening.