Electronic Psychotherapies and Cognitive Remediation

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[MUSIC] Welcome to the panel on electronics psychotherapies and cognitive remediation. My name is Beth Twamley. I'm a Professor of Psychiatry here at UCSD. It is my wonderful job today to introduce our two speakers. First up, we will have Dr. Tarik Rajji.

He is a Professor of Psychiatry at the University of Toronto, where he serves as the Chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at the Center for Addiction and Mental Health. He's the Canada Research Chair in Neuro-stimulation for Cognitive Disorders and he's also the Executive Director of the Toronto Dementia Research Alliance. He wanted you to know a fun fact on aging. Grandma Moses, the famous American painter started her painting career at age 78.

Pretty impressive. He will be speaking with us today about neuro-stimulation for cognition and Alzheimer's dementia and high-risk populations. After that, we will have Dr. John Torous, a graduate of the UCSD School of Medicine. He's currently an assistant professor of psychiatry at Harvard Medical School. Since he came from UCSD, we take credit for everything he's done.

He's the Director of the Division of Digital Psychiatry at Beth Israel Deaconess Medical Center. His research in clinical work focuses on using mobile technology to help advance care for people with serious mental illness. His earliest work included reports on how older adults are interested and engaged with new health technologies and his ongoing efforts highlight the potential of mental health innovations for all age groups. Dr. Rajji, take it away.

Hello, and thank you very much for the invitation. Thank you Beth for the great introduction. The focus of my presentation will be on showing you some of the trials we're doing on combining advanced simulation with interventions , specifically cognitive remediation. Just as a disclosure specific to this presentation, the two trials I'll be talking about, we've had some in-kind support. One is from SVD pro for the cognitive remediation online program, and the second is online in-kind support for the TDCS machines that we're using for that combination of MBSR plus TDCS. I don't think I need to convince this audience about the heavy weight of Alzheimer's dementia and dementia in general and worldwide, including in the US where more than six million people now live with Alzheimer dementia and one in three people die with Alzheimer's dementia or another form of dementia.

As you know, despite some of the recent advances and some of the approvals, I think still it's very hard to treat and make a major change in trajectory once the dementia stage of the illness is in set. That's why we and others, as you can imagine, we've been focusing on earlier stages or high-risk conditions that increase the risk of developing dementia. Two particular conditions or stages that we focus on in our studies, in particular, the trial that I'll be talking a lot about today, one is MCI, which has mild cognitive impairment, which these are individuals who have deficits on objective tests, on paper and pencil test, for example, they're still living independently.

Those individuals are at significantly higher risk of developing dementia over time. The second condition that's also has been more recently known that it significantly increases the risk of developing dementia is having a history of depression. This is related.

You all know meta-analysis is showing prospectively that people who have history of depression in late life, they are a double the risk of developing dementia. We've been focusing on these two conditions to deliver interventions or try to prevent cognitive decline and the manifestation of a syndrome of dementia where functional impairment is manifested. The conceptual framework that guides a lot of our interventions is focusing on compensatory mechanisms to try to prevent cognitive decline. This is one of the earlier models that was proposed and talked about where aging and to that effect also disease-related mechanisms affect certain networks and certain function specific.

In compensation for that, this model suggests that some association cortices like the prefrontal cortex, sets in and contributes to compensatory cognitive mechanisms that could delay overall cognitive decline. Our studies are designed in a way that we believe aim at improving prefrontal cortical function and to optimize and increase compensatory mechanisms so that we can prevent cognitive decline and dementia in people with high risk conditions. The study that I'll be talking more about the next few slides is called PACt-MD, or preventing Alzheimer's dementia with cognitive remediation.

Plus tDCS, or transcranial direct current simulation in MCI and depression. It's a multi-site study. In Canada, the sites are in Toronto and they're funded in Toronto across several academic hospitals, funded by the bank and the foundation.

What is tDCS? TDCS is technologic as a simple tool that delivers direct current, low voltage two milliamp current that is direct current simulation using an anode and the cathode. That's for the actual machine from maximum neuronican developers. You can see the two, these are the sponges that are placed depending on the location where excitation or inhibition is meant to happen. I use this term loosely, even though we know that the natural reacts maybe differently. But just for the sake of presentation today, the concept is that there is excitation where the anode is placed, which in our case we place it over the prefrontal cortex.

There is the reference where there's inhibition is under the cathode, which were replaced at the back of the [inaudible] side. This is going to force the tension used and experimented throughout history. This is a photo of the Egyptian Nile catfish where people used to be asked to put their feet in the liver and maybe try to treat arthritis or pain.

Some of the early physicians from the early Arab world where they used some electrical shock from fish to try to treat melancholy or epilepsy and migraine. How does tDCS work? TDCS unlike TMS, when you deliver a transcranial magnetic stimulation or TMS, let's say the motor cortex that is related to the hand muscles, for example, you see a twitch of the thumb, you see a which of the hand. It does generate action potentials from the motor cortex, that's where it's the simulation is happening.

TDCS does not result in this switching. Believes that it doesn't result in action potential in activation firing of the neuron. But the thought is that based on pre-clinical work, is that it changes the resting membrane threshold of the underlying cortex so that this network or that particular cortex becomes more likely to respond to another intervention and more likely to result in longer-lasting neuroplasticity changes. The early studies of tDCS in the human, were like many brain stimulation studies, were done over the motor cortex.

This is one of the earlier studies showing how after delivering tDCS for different periods here on the x-axis, you see the number of minutes that you start seeing potentiation and response to TMS for that other intervention. More sustained potentiation, more sustained enhancement of the motor evoked potential. That's the activation from the hand muscle in response to TMS. We're after stimulation using tDCS and that is an order of tDCS.

This is how one of the earliest experiment showing how tDCS could promote neuroplasticity in this case in the motor cortex. At the time when we wrote the grant, also, this is one of the studies showing tDCS impact in patients with Alzheimer dementia and showing some potential benefit here for small studies with N of 15. The delivery here was using bitemporal, so two temporal cortices of anodal tDCS and increasing potentially number of correct responses on a memory task. This also early study with tDCS where supporting the idea that it's best used when it's combined with another intervention.

This experiment, what was done comparing tDCS delivered during the performance of a working memory task. Specifically the n-back task in people who have depression. That's the online stimulation versus delivering tDCS before the performance on the n-back task, and in comparing sham versus active tDCS. What was shown in this study is that performance improved when the simulation was happening concomitantly during the delivery of the call back task. Thinking the evidence and there is some more evidence all the time to go over that at the time when we propose the study.

Putting all that together, we propose that you would like to enroll individuals who have a high risk of developing dementia, particularly people with MCI or depression and depression with or without MCI and deliver to them in acute course of a combination of tDCS that was delivered in combination with cognitive remediation. I'll explain a little bit more what the design of the intervention is. With the idea that with the tDCS, we're changing the threshold of stimulation so the network becomes more responsive to the cognitive remediation. Therefore, believing that the individual tools will then benefit more from the cognitive remediation by priming their network using the tDCS. Again, going back to the model where we want to target the prefrontal cortex and a target more top-down processes so that we promote competence.

The remediation approach that we're using in this trial, led by Dr. Christopher buoy, focuses a lot not only on drill and practice, but also strategic learning and promoting the transfer of the learnings that happened during cognitive remediation session where people are doing the computerized exercises. During that session there is a therapist and preventionists where they are leading a discussion and supporting the participants to how to transfer the learnings and the strategies are learning from resolving those computerized training to the real-world function. That's strategic learning we believe is also promoting that top-down processes that will be optimized in this study that's at is the model optimized using the brain stimulation. These are the eligibility criteria for the participants under trial. To the group of the MCI, they had to be age 60 and meet the DSM-5 criteria for MCR, mild neurocognitive disorder.

With the depression group with or without MCI, they had to be 65 and above. They had to meet the criteria of DSM-5 for MDD, but they have to be in remission when they participate. The idea is that we don't want to focus on the cognitive function impairment that is related to the acute state of depression.

But people had to be in remission and still are at risk, will believe that they are still at risk even though they are at depression we know that they are at risk to developing dementia, whether they have MCI or automatic. That's the overall design of the actual intervention. People get randomized to active cognitive mediation plus active tDCS versus sham-sham. Maybe in the discussion, we can discuss the pros and cons of this design. What is Sham called remediation? The key differences is that one, there is no titration of difficult pieces when people and the active, when people reach, let's say 80 percent of correct performance, they get more challenge. There is more neuroplasticity driven processes in place.

Also there is no focused on that transfer of information, transfer of the gains from the cognitive remediation to real world. The sham tDCS, is based on the fact that they would only get about a minute of simulation. There's a ramp up and ramp down. People get the sensation of tingling sometimes that happens with the tDCS, but then after that there is no current being delivered. There is an acute phase which where people come to classes as a group up to eight people in a classroom. It's five days a week for eight weeks.

Then after that, all participants are asked to engage in cognitive remediation from home remotely, at least 20 minutes a day. Then they come back for booster sessions every six months for one week they get five days of combination of tDCS versus cognitive remediation. That goes on until the end of the study or until they progress to developing either from normal cognition to MCI or dementia or from MCI to dementia.

The whole study is a seven-year study and we are in the final year of the study so now people are wrapping up. I'll show you the fluid room recruitment and where we are in the study, but we don't have to find that results yet. The plan is to analyze all and have the results next year. There was a significant longitudinal follow-up between 3-7 years based on when people started the trial. That's the schedule of the assessments.

They get assessment that baseline. They get the first follow up after the acute phase, which is after the eight weeks, then after that its yearly assessment to determine whether personal progress cognitively or two-dimensional to MCI. These are our hypotheses.

The first hypothesis is about cognitive decline over the whole period of the trial. It's using the continuous measure and then second hypothesis about categorical measure of developing depression. We could change acutely after the eight-week intervention, irrespective of the impact on longitudinally over the seven-year study. That's our floor to date so we finished recruitment as I mentioned, widen the past few months of the study.

As you can see it, we pre-screened a lot of people, more than 1,400 people. The final sample here is we have 200 people with MCI, 80 people with NADD plus MCI and 95 MDD without MCI. What's been exciting is that retention of the study has been very high and the 80 percent range over the trial.

Last couple of slides that we're adopting this approach of combining these tests with other intervention, with other forms of dementia other than cognitive remediation. In a pilot study that we conducted and collaboration with Lancet. We combine tDCS with MBSR, mindfulness-based stress reduction. Where Eric and his team have shown that in older people with depressive symptoms and anxiety symptoms, it could have an impact on cognition and memory specifically. In a feasibility study, we tried to combine tDCS. Delivering tDCS, receiving it while doing MBSR.

We learned a lot about the challenges of doing that. Now we're thinking about what could the project look like to optimize the use of tDCS, during MBSR. But from an early signal why we were still interested in pursuing this line of work. It seems that those who receive the active tDCS everyone received MBSR. But those who received the active MBSR seem to have learned mindfulness better than those who received the sham tDCS.

There was some signal on depressive symptoms, anxiety symptoms, and some measures of quality of life. Again, this is a pilot. None of these were statistically significant, but there was a pattern that was encouraging for us to pursue further and that's it. That's all my presentation. I want to thank you for the invitation. Thank all the audience here.

These are my collaborators, are the PIs on the PaCt-MD study, and many other collaborators and funding agencies who supported this work over the years. Thank you. Thank you so much, Dr. Rajji for a great talk and also for staying on time. Very much appreciated. Next we'll switch over to Dr. Torres,

who will be telling us about how to evaluate risk and benefit for electronic psychotherapies and cognitive remediation. Dr. Torres. Thank you so much, Dr. Justin and everyone at

UCSD for inviting me. As was briefly mentioned, I graduated from UCSD School of Medicine 10 years ago seems not that long ago, but I still do a lot of work actually with UCSD at such a fantastic place to collaborate. It was a couple years guys doing some design work at UCSD, and this year with Dr. Justin, his team, we actually wrote a paper on artificial intelligence for mental health care. It's hard to not work with UCSD and especially around aging work because it's all happening here so I'm glad I got to be part of the UCSD family, but I'm still actively collaborating. A lot of what we'll talk about today is work that has parts of UCSD that we'll talk about.

But so in essence, what we're going to talk about is mental health smartphone apps. You've probably seen these being advertised to you now, you may have heard of them, many people who have tried them themselves. They're becoming more and more prevalent. The question we want to answer is, how do you know which ones are good? How do you know which ones are not good? Which are safe, which are effective? What can you do? A little bit of a spoiler alert for those of you watching on a computer right now, you can go to mindapps.org and we're going to show you how we built this database of mental health apps, why we built it, and how you can use it to find mental health apps that may be useful, effective for you.

In this talk that plan is not to endorse any product, it's not to say anyone is bad. Any examples I mention are educational. When you think of mental health apps, there's almost two broad categories.

One is going to be self-help apps, could you use brain training games to put your cognitive performance you can do at your own? Could you use a therapy app to do skills to help yourself feel better? There's a lot of self-help apps out there. There's also apps you can use in conjunction with clinicians as part of your team. This is actually a screenshot from the Wall Street Journal today, if any of you subscribe to Wall Street Journal, you'll find this exact picture in your newspaper. It talks about how here at Harvard, how our team is using apps in conjunction with patients to extend the therapy visits.

Again, if anyone gets a Wall Street Journal, this picture is just out as of today, as of nine O'clock on East Coast Time, so you may recognize this. But a lot of what we were talking about is self-help app. If someone says, hey, here's an app that can improve your mood, here's an app that you could use for therapy, here's an app to improve your brain functioning, how do you know what to do with it? Is it good? Is it bad? Usually the first thing we would think of, well, is it FDA approved. That's a little bit tricky in the mental health entire software space.

This is a quote from a paper that was actually done two years ago and I'll explain to you why it's still true, but says consensus among relevant form participants was that FDA clearance, which focuses on safety and minimal effective thresholds, does not provide adequate information for decision-makers. The point being, the way that the FDA is approaching software is exciting but it really is not the same way to approaching say, drugs or therapy. Even if an app or software says it's FDA approved, that may mean something, but it's not going to guarantee you're getting the best product. If this slide looks complicated, in part it is because this just shows you what the regulatory landscape looks like for this software today. The main point I want to say is when someone brings you an app, the app developer, not your clinician, not you, can just call it a wellness app. If they call it a wellness app, there's really no regulation that takes hold.

You can make an app that looks medical, it says its going to do brain training, it says this is going to help you think better, it's going to help with mood but it's just a wellness app. There's no protections, just no guarantees. Is like buying vitamins at the drugstore.

They can make a lot of claims on it. Look it's tricky for us in the brain training in the mental health space as the FDA has a lot of buckets called enforcement discretion, which is a technical term. But the FDA says, well, a lot of apps that fall under certain categories, like offer much of the day, offer mental health advice don't really need to be actively regulated because we think they're low risk. A lot of apps for the mental health space don't really fall under the FDA's oversight.

To give you an example of this again, all examples are just uses educational, during the height of COVID, in April 2020, the FDA said we're going to even loosen regulation around what they called digital health devices for treating psychiatric disorders. Recently the FDA said we may make those loosened regulations more permanent. What does that mean to you and me? This is a headline from July of this year. It says this company plans to roll-out, a digital therapeutic for anxiety and depression under temporary FDA guidance. It says the company is making its app based treatment available to patients, thanks to loosening the FDA guidance last year, that lets digital health companies targeting some behavioral health conditions like the ones we're talking about here and all today, released their products without clearance.

The company is launching investigation on site to get data for future FDA submission. You can see how it's really tricky to know when someone says FDA is that for the future, what does it mean? Is it exempt? The situation in some ways is actually so wild that the Federal Trade Commission, the FTC, not to FDA, the FTC stepped in and they said they're going to start perhaps enforcing privacy rules in regulating the space a little bit more or so, you can see it. It's an evolving landscape.

This is not September 15th of 2020. This is just a couple days ago or last month. It's not the first time the Federal Trade Commission has stepped in.

I think especially relevant, it was about five years ago, but if anyone remembers Lumosity, the app that was doing brain training used to advertise a lot on the radio, on NPR. They actually got fined by the Federal Trade Commission for deceptive advertising because the FTC said, I'll summarize it, they implied that they could reverse some of the effects of cognitive decline or illness like Alzheimer's that clearly again, we've seen all the great research they happening, but sometimes an app is not going to fix everything. We know that, but the company had to retract since advertising. That said, our team was entrusted in this and we know that Lumosity, many apps that offer brain training. This was a survey we did up to market share and we just saw a lot of people using the Lumosity.

It doesn't mean that it's better, it doesn't mean that it's worse, but again, it's just interest rate. The one that had the most market share, had most advertising, was actually the one that got sued by the FTC. If you're saying, John, what do I do? The FDA hasn't given me a clear indication, the FTC is stepping and I'd like to use one of these apps, what comes next? In part, we've done work with the actually American Psychiatric Association. With the American Psychiatric Association, we built a pretty simple framework that you can use to look at an app and say, is that going to be useful for me? You can use this to talk with your clinician. Say let's think about the factors from app that matter to me or to realize what apps are not right for you.

Even if you just google APA app evaluation, we have a lot of videos and tutorials are completely free to go through. There's no one product recommended. But what I want to do is take you through these layers of what is the potential risk in using one of these apps, what is the potential evidence for them in general, we'll talk about are they easy to use? We'll talk about what we know about does the data get back and use, or is it clinically meaningful? We'll summarize how we turn this into the website, mindapps.org so you can search a lot of these apps today and look what's out there. But this is actually a picture from the magazine consumer reports.

[MUSIC] Some of you may get it, it usually rates toasters and toothbrushes. Sometimes they rate cars. They actually in January, this year rated mental health apps and they selected these apps.

But this is actually a picture and they basically asked questions about the privacy practices of these apps. What Consumer Reports found was that a lot of these apps aren't getting green. They're not doing great privacy things with your data. That's a little bit concerning. You say, Well, how are they getting away of not protecting my privacy? As we talked about earlier, they say they are a wellness thing, they don't have to follow any laws or guidance or there's no way to enforce it. It's not just that mental health apps are having some issues around privacy.

This was a paper from June of this year and it said that 47 percent of user data transmission in apps across the whole digital health space are beyond mental health but 47 percent compliant to a privacy policy. That means 53 percent did not. It's a little bit concerning. I think before using any app, I think I would just recommend talking to your clinician, whoever you work with because there can be quite potential iatrogenic effects. This meaning that if you're doing something like an unguided exposure therapy without some help, sometimes that can be harmful. With actually a complete UCSD team, I highlight their names here, I was fortunate to join them in May of this year.

With Emma Parrish and Collin Depp and Renee Moore and Camille Nebeker from UCSD, we actually looked at the crisis management in these apps. What do they do when you're not feeling well, when you're feeling unsafe? We found these apps have a lot of gaps in it. We get a good reason why you want to talk to someone about using an app and not automatically sign up, even for the self helplines. It's just a nice example of terrific research from [NOISE] UCSD that's leading the way in making sure these apps become more safe. In terms of the second level, again, how evidence-based are this apps, clearly want to use something that's going to make you better.

In a different study, we went to the iTunes and Android store, which I've read those App Store descriptions. We coded, does the app make a claim? Does it say you will get better job? Does it say your anxiety will be less? We found that 64 percent made supporting statements. But we went back to the scientific papers and looked at it and said, what is the evidence with only about 1.4%? We've found that app sometimes aren't completely honest in what they're saying or their claims are a little bit exaggerated. A lot of popular apps, you may have heard of the term CBT, cognitive behavioral therapy, a very effective therapy. How does it work when it's delivered on an app? What we found and other reviews have found too is, clearly we know, cognitive behavioral therapy, if you're doing it in person or you're doing on a live video visit with a therapist is very effective.

But if you're perhaps doing it yourself on the smart phone, we don't know as much. It's a new way of delivering therapy. Let's say if we know that the book was great, is the movie going to be good? Sometimes, sometimes, no. In this review, there wasn't very much evidence.

Only 6 percent were often a randomized controlled trial of these apps. Most of them weren't dealing with suicide or helping understand risks around depression well. A lot of them were offering non evidence-based techniques, so something that's not great.

If you're interested around the evidence of apps, this summer our team wrote a article called Should Your Company Provide Mental Health Apps to Employees? I realize we're not companies, we're all individuals listening. The same principles actually will relate to this. Again, it's a free article you can download from Harvard Business Review, but you can just replace should you use mental health out yourself.

You can look at the evidence and say, is it right for me? I think one of the most important things to consider when using any mental health app, someone says, here's a new brain training app, here is a new medication tracking app, is it going to be engaging? Is it something that you feel that you can stick with? The most comprehensive evidence from across America, from a large study had these grassroots said, if someone downloads an app and we look five days from when they started using it, ten days from they started using it, how likely are they to keep using it? You can see that after two days, about 60 percent of people will stop using it, and after 10 days, about 90 percent of people will stop using it. This doesn't mean that apps can't be engaging, of course, we know many people like to use them for months and for years, but, it's not as easy as downloading an app and then you're going to be motivated to use it every day. We all know that a behavior change is hard. We know that cognitive remediation is hard, therapy is work.

We have to change our habits, we have to change our behaviors, and we change our thoughts. Sometimes it's useful to remember how using an app is like having the equivalent of a gym body. It's worth telling your condition, getting some support around it because even the most engaging apps today, sometimes always are not super engaging. The last point in thinking about would you want to use an app or not is really to say, you don't want to it just to be collecting data, so it goes into a Data Silo and fragments to mental health care. You don't want to have to go to a clinician, say, I keep my medication data here and my therapy data here.

My stop counting data here, my diet data here. That's not useful. You want apps and technology that let things integrate. It goes into the epic medical record at UCSD. It brings your step count directly in, it records it.

Some apps offer that, but some apps don't. If you think about so, we very quickly review these levels of, again, what is the privacy and security app? What is the clinical foundation? What is engagement? What is a therapeutical? Why are you using it? These are four broad categories, but especially important to think about, we put privacy first because again, sometimes we don't think about that one, say doing therapy or starting medication. Again, on the American Psychiatric Association website, we have lots of questions and tools to help you guide through this. We actually have a panel that keeps updating these questions, making sure it's relevant. We've included nurse practitioners, social workers, therapists, peer specialists, students.

A lot of different people to make sure we represent diverse viewpoints. We have office hours every month for anyone, you don't have to be a doctor, can bring questions about apps. But the feedback we got is people said, well, this foundation of how to look for an app and to make sure things are private and safe and effective makes sense, but I don't have time to do that or I may not have the expertise. Our team did a project to turn those principles of app evaluation into a database that anyone in the world can search.

Again, whether you're a doctor, whether you're a patient, whether you're a family member. The first challenge we have is what we said, how do we code in a database, something you can look up? Is it easy to use for you? Because we don't know who you are. We said, well instead of saying is the app easy to use, let's think about a thing we can code as yes or no. They're searchable by a computer, so you can search it. We said, well, let's code, does the app offer video? yes or no? Does it offer music and audio? Yes or no? Does it offer gamification away to app to make apps engaging for some people? Yes or no? The idea was, we said if we could code enough features of apps could not be a good way to search for apps.

The hidden message is we don't want people to search for apps based on the number of stars, number downloads. Just because an app has a lot of stars doesn't mean much. Again, you're not going to look for a therapist probably based on stars on Yelp. You're not going to pick a medication by going on the Internet and seeing which has the most reviews.

You want to ask the clinically meaningful questions. The idea of the database is, could you pick apps based on features that are clinically meaningful instead of having to rely on stars. We did the research and turned these principles into a database. The database is called MindApps.org and supported by a charitable gift from Argosy foundation.

There's no commercial interests, there's no conflicts of interest around it. What you can do is you can type in, say well, I have an iPhone, I'm looking for an app that is brain training. I want to be completely free and I want these privacy features.

What the database will do is, It'll come back and say, here's some apps that meet your criteria and you can explore those. It'll quickly help you narrow it down. It won't tell you one app is good or bad. The database has been featured in the LA times. You can see it said the headline was, need a mental health app, there are apps for that, but picking one is tough.

It was between Popular Science, mental wellness apps so basically [inaudible] therapy and talks about mind apps can offer information to help you filter it. Even Cosmopolitan the magazine said this could be a useful tool for people picking apps they want. How the website works, since there's filters, you can say supported conditions and you can pick which one you want. You can say, I want an app to help with sleep.

I want an app to help with mood disorders. I want an app to help with my thinking, and then there's a filter for costs. They want an app that is totally free again, depending on what you put into it, the database will show you what comes out of it. As one example of how you could use it, say while I want an app that it's totally free, I want the feature to be mindfulness and I want the functionality to be offline. By that it works if you don't have internet access.

It works in airplane mode because not all of us have unlimited data. That I may come back. They say well, I want an app that's totally free, that helps me with PTSD and for privacy, I want the data stored on the device. What it would do is come back with this app. It's a fun thing to search. I encourage you to look at it. If you find many apps that we don't have, I would love it if you email me.

We'll get those apps rated. If we made any errors, there's actually each app says fix anything right now, and you can let us know. Hopefully, you understand a little bit about the pros and cons of picking apps and can use this as a resource to make good decisions for yourself. Thank you.

Thank you so much Dr. Torres. That was a great talk and really great information for consumers to be aware of. Thank you. Let's kick off the questions and answers. Dr. Rajji, I see that you already answered some of the questions about TDCS compared with electro-convulsive therapy, but I think it might be worth having just a quick primer on those modalities. There's also a question comparing to RTMS and what conditions do they treat? Yes, there's a.

Thank you. There were some questions about the comparing is TDCS the same as ECT or what's the similarities? It's not the same, ECT requires people to be anesthetized, they are not awake. TDCS is delivered while the individual is awake, as I mentioned, they are able actually to engage in other activities. For example, cognitive training or order mindfulness, MBSR, Mindfulness-Based Stress Reduction. It doesn't cause seizures, so ECP the way it works, it causes seizures, unlike ECS does not cause seizure. RTMS is another form of brain stimulation that's used on delivering magnetic stimulation versus electrical stimulation, which is the case of TDCS.

Some of the difference I mentioned that RTMS which is approved actually in the US for the clinical depression. TDCS is still not approved for certain conditions. Some of the differences is that RTMS is compared to these, TDCS are thought to activate the brain to cause firing of the neurons, firing of those brain cells.

But there is some similarity. It's more focal, for example, the RTMS than TDCS, sometimes you want to be less focal depending on the design of the study. Although there are approaches, there are methods of where TDCS can become more focal with what we call high definition. TDCS, one big difference also that TDCS is portable, but people can be delivered at home. Some of the work we're doing is like the MBSR one where we combine it with MBSR.

People take the machine with them at home and learn how to deliver TDCS on their own. While doing the mindfulness training. RTMS, most of RTMS studies on machines, people have to go to a center to get the RTMS treatment. I think I'll stop here. Thank you. Another question came in. I think this was meant for Dr. Torous, but Dr. Rajji, you may have an opinion on this too.

What do you know or what do you think about posit science brain HQ? I think all of them roughly have the same evidence. There's not clear data to say one is better than the other, I think the best thing would be to talk with your clinician about what you hope to get from it. But also probably depict the one that you think is the most engaging that you can stick with it. We talked about engagement is one of the hardest things in this.

To make sure it really is at a price point you care about to look at it. But I think I would first talk with your clinician or treater to say like, what are you hoping to get from it? Sometimes these apps could do something, but again, they don't have always the strongest evidence for say, transforming how you're thinking. But sometimes they can offer benefit. Dr. Rajji, any opinions on posit science, brain HQ? Nothing specific about that particular program, but I think one of the key point is also as making those decisions comparing is the ability or comparing the benefits in the transfer of the gains that are learned from these training system to the real-world functions.

I think that's one of the still the challenges across the field. I think that there are many, there's some evidence for certain programs versus others. Programs that don't need a therapist present or interventionists versus others that do require that.

Thanks. Can you recommend an app for happiness, Dr. Torous? I cannot, but I can say if you go to mind apps and putting mood and you put it in free, which is always a good filter. You can actually see what's around.

The other reason it's tricky is the apps update a lot. We didn't talk about, but if you have an AV smartphone apps, you realized they change a lot. Everything on the database every a 180 days, we recycle it much sooner.

I think in one way, it's just good to see what's around today and go for it. But you've actually, again, there's a lot you can explore and I think I would just check my personal bias to check all the privacy features and to check for the lowest cost, and you may actually quickly find the app that you want. Great, Thanks. A question about the security vulnerabilities of these apps if they're linking to patient records. There was recently a huge security breach at UCSD, as you may know, and confidential patient data were released in that breach.

Are these risks applicable to some of these apps? I think anything with the digital world, even with online banking, there's always some risk of data going away, even if medical records, I think every hospital in the world has had some type of hacking to some degree. I think what you want to do, is understand what the risks are of those apps and what it does. Again, we talked about there's ways to check what those features are.

I'll sound like a broken record, but at least you can look in that database and say what are the 10 security features that offer? You can at least minimize your risk by go with an app that offers you to most things. A lot of the apps that we have no doubts are made by the Veterans Administration, the VA, and they actually don't take the data off your device. Anything you put on it, it just stays on your phone.

We actually have a filter called Keep. Show me only apps where my data never leaves my own smartphone. For many people that can be a good choice. The VA, the only apps I'm allowed to endorse by my hospital is the ones from the VA cause it's the federal government and are completely free and there's no sales pitch. If you're worried about that, you can definitely find ones where the data is only on your phone. Yeah, I agree. The VA has really put a lot

of resources into developing some really great apps. They're engaging, they look good and the privacy features are are good and they're all free. Yeah. Great. Thank you. I have a question for you, Dr. Rajji, is it too late to

intervene if a person already has Alzheimer's disease? No, I think it depends on what intervention I think. There is always, of course, we try to intervene early, but I think depending on what stages and what are we trying to target one individual that would be my approach is that what are we targeting? Are we retargeting compensatory mechanisms where people have early Alzheimer, dementia. Once people have developed a stage.

As we know, the disease starts very many years earlier than the actual manifestation, the clinical manifestations of the disease. If we're using compensatory based interventions, then it may never be too late except maybe at the very advanced stages. But then also we need to maybe as we know, Alzheimer's is not just about memory and it's not just about cognition. We also need to think about the different neuro psychiatric symptoms, behavioral symptoms, responsive behavior, and what interventions are suitable at those stages. There's always hope for intervening at all different stages, I believe. Yes, I have another question which is, you both are psychiatrists and I imagine that you see a fair number of individuals who come in with maybe some anxiety and depressive symptoms.

Maybe they're concerned about their cognition, but they haven't been tested yet. It doesn't seem like they have dementia but they have some concerns. I imagine this is a typical patient. What do you offer first and how do you make those decisions about what treatment would be right for that typical patient? Dr. Torous, you're unmuted. Why don't you go first? I think one thing that's certainly we do is always evaluate people for depression and anxiety. Because we know that if we can treat the depression and anxiety, certainly there's cognitive effects of having severe depression.

There's cognitive effects of having severe anxiety. We also look at sleep, we know intuitively that sleep is related to how clearly we're thinking. But sometimes it can actually be tricky to understand how good our sleep is. There's actually a very famous case report by Dr. Ipsit Vahia who is at UC San Diego, who was actually using wearable sensors to understand how people's sleep was impacting their depression and that it looked like all timers versus depression, and actually by using wearable sensors Dr.

Ipsit Vahia when he's working with the senior behavioral unit, was actually able to show that you can really differentiate the two. But in some ways, we know again that cognition can be related to depression, advice. We want to treat those as best we can, optimize care. Oftentimes we get good success there, not always, but I think it's something that, again, we can treat well, we can evaluate, and of course, we want to rule out sleep disturbances or issues first. Which we can do, we don't always need technology, but again, I think it's a nice no UCSD example of using those wearable devices to help learn about what's happening. I'll push you a little bit more.

How likely are you to recommend an app for our typical patient? For most patients, how we recommend apps is that we're doing our in-person or video visits that are right live. But what we're doing is we're thinking about what skill do we want someone to work on outside of the session? Do we want someone to practice a sleep skill? Do we want someone to be tracking how they're sleeping? What information we want to collect? The model that we like to use is we're going to add each session considering, not always need to, but is there new data or new skill to practice outside the session? Can a wearable or technology make it easy to practice that skill or collect that data? But we're only going to do it if we have a plan to next session of what's going to happen to that data or that skill. We're going to check in and say, how was it practicing a new thought patterns skill? What did we learn about looking at your mood over time? What did we learn about looking at your step count? I think when we make sure we integrate it into the treatment plan, it's not that we're collecting the same data on every person all the time. It's we're saying we know that the clinical visit, our face-to-face session is less than 0.1 percent of your entire month if we're seeing you once a month.

There's a lot of stuff happening outside and with your permission, let's learn more about your lived experience, what's happening to you. We found that the nice model to do. We're usually customizing things for each person based on their needs. Certainly, some people don't want to use any technology and that's perfectly wonderful. Just like some people don't want to use certain medications, some people don't want to try things that most people are.

I think that we're pretty excited about that model because in some ways it enables us to deliver a very personalized care and very patient-centered care. I love that evidence-based approach to care. Perfect. Dr. Rajji, I'll put you on the spot.

What do you think we should do with this average patient? Are you going to recommend TDCS? Not, well I would recommend participating in studies, but I don't think there's evidence yet for clinical, but I think I would, I completely agree with Dr.Torous about the approach, doing comprehensive assessments. The one thing I also have a discussion usually especially if there is cognitive concern or is that concept of MBI or mild behavioral impairment, which is an evolving concept that sometimes the neurodegenerative disease may manifest itself early on with behavioral symptoms, not necessarily only cognitive symptoms. That's in contrast to the NCI. Why is important to focus on that, because that emphasizes the point of monitoring cognition, monitoring trajectory, not just treating the symptoms of behavior some, but also having a plan for longitudinal follow up to catch any functional decline over time.

The other key discussion I have usually with individual presenting in this syndrome in a way that's focusing on lifestyle. Despite that the evidence for intervention continues to be buried, the epidemiological evidence linking some of what we call now potentially modifiable risk factors for dementia is really significant. Thinking about, is my patient engaged socially? Are they engaged physically? Are they active cognitively? Are the symptoms of depression addressed? What's their smoking status? Are they taking care of their hypertension, diabetes, isolation, the loneliness like we just talked about? It's always amazing to me how having sometimes, and these are things many times the patients know about, that sometimes common sense.

But actually having that conversation in the clinic somehow triggers that the momentum of making a change. I talk about it as if it's a prescription so next time I want to see you in a month or two, I would like to tell me how many visits you've had, how many social social events you've had with your friends that you haven't seen for or you're thinking about seeing over the last year or two. I approach those lifestyle potential changes in a systematic ways, same way we do with medications and our other intervention. I've even seen clinicians write on a prescription pad, play cards with your friends.

There are a couple of questions coming in about anxiety and depression. When you're assessing these, do you count life issues like death and divorce and so on? Also, I think you've answered this partly with your answer about behavioral lifestyle modifications, but can you treat these conditions with non-medication therapies? [OVERLAPPING] Either of you who wants to answer that? I'll start. You can definitely start. You can often treat them without medication, sometimes you do need them. But I think what's exciting is that in some ways technology can help us increase access to therapy and care. That if we know it can be effective or everyone has the potential to perhaps try it or get personalized therapy through technology. I showed you, we're still learning about.

When it works, to answer part a question, certainly we know there's something called adjustment disorders in mental health. We go through big stressors, maybe young people going to college, you send the question there, death or divorce, those are really stressful periods and the body will react to them. We always want to be careful when we're understanding to say, well, is that adjustment disorder when the stressor goes away when the pain about loss gets less? Will there be less symptoms? Again, you don't want to pick up an app, that's why you still want to work with professional. The app is a good treatment plan or tool once you know what's happening. But you don't want to say, well, I had this new stress so now I'm going to use an app because there may be a reason. It's a natural reaction to a very broad situation and you don't need to be doing one of these things or you don't want to get into lifetime subscription for therapy [LAUGHTER] app that keeps going year after year and just billing you.

But there could be cases where you want to work with your provider and say, "Hey, this is a great way to learn extra skills, to hopefully feel better, quicker." But the answer is, we can definitely try with therapies and apps can help with therapy but we want to make sure that we're using at the right time. Because there's reasons, as you pointed out in your question, that we may not be something we want to treat right away Thank you, Dr. Rajji and Dr. Torous for a great panel. Really appreciated your insights this morning. Thank you very much. [MUSIC]

2021-11-11

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