ISTAART Relay Podcast – Reserve, Resilience & Protective Factors PIA

Voice Over:

Hello, and thank you for tuning into the third season of the ISTAART PIA Relay Podcast, brought to you by Dementia Researcher. ISTAART is a professional society and part of the Alzheimer’s Association representing scientists, physicians, and other Dementia professionals active in researching and understanding the causes and treatments of Alzheimer’s Disease and other Dementias.

Voice Over:

In this five-part series we’ve, once again, asked members of the ISTAART Professional Interest Areas to take turns at interviewing their colleagues and being interviewed themselves, with the interviewee going on to be the interviewer of the next episode.

Voice Over:

We’ll be releasing one of these podcasts each day in the build up to the Alzheimer’s Association International Conference to showcase the amazing work of the ISTAART PIAs. So, this week you’re going to hear all about fluid biomarkers, atypical Alzheimer’s Disease, reserve, resilience, protective factors, immunity and neuro degeneration and technology in Dementia with some amazing guests.

Dr Rik Ossenkoppele:

Hello, everyone. Thanks for joining us. My name is Rik Ossenkoppele and I’m Associate Professor of Translational Neuroscience. And I work at the Amsterdam University Medical Center in the Netherlands and at Lund University in Sweden.

Dr Rik Ossenkoppele:

I’m also the vice chair of the Atypical Alzheimer’s Disease Professional Interest Area. And today, I’m delighted to be talking with Hamid Sohrabi. Hello, Hamid. It’s a real great pleasure to meet you.

Dr Hamid Sohrabi:

Hello, Rik. Thank you. The same here.

Dr Rik Ossenkoppele:

Can I start by asking you to introduce yourself and tell us which Professional Interest Area you are involved with?

Dr Hamid Sohrabi:

Sure. I’m an associate professor of Psychology and Neuroscience, and I’m based at Murdoch University in Western Australia where I’m leading the Center for Healthy Aging. I’m also a sitting committee member for the reserve, resilience, protective factors for the Alzheimer’s Association ISTAART PIA. So very happy to be talking about our PIA today.

Dr Rik Ossenkoppele:

Yeah, I’m looking forward to it as well. So, before we jump into the topic, I want to learn a little bit more about yourself first. So, can you maybe tell me what brought you to Dementia research?

Dr Hamid Sohrabi:

Sure. I started my research back in 1990 when I was doing a Master’s in psychology, in clinical psychology to be exact. And for my thesis, I was working on memory performances in schizophrenia and brain injury.

Dr Hamid Sohrabi:

So, my love for memory research goes back to many years ago, but I hadn’t started Dementia research until I got to migrate to Australia in 2004. And then a couple of years later, in 2006, I started my PhD here in Australia that I started the project on identifying the risk factors as well as new measures for identifying those who are at risk of Alzheimer’s Disease.

Dr Hamid Sohrabi:

So, the background in Dementia research goes back to about maybe 16, 17 years ago. Since then, I’ve been delighted to work on developing novel measures for identifying those who are at risk of Dementia, as well as investigating psychological and modifiable risk factors, lifestyle risk factors for Dementia.

Dr Rik Ossenkoppele:

Right. And given your role in this Professional Interest Area, I assume your current research is also strongly focused on protective factors against Dementia or Alzheimer’s Disease particularly?

Dr Hamid Sohrabi:

It is. Yes, of course. That’s a great comment. My main area currently is to look into lifestyle factors from single to multimodal interventions and see if we can potentially delay or prevent risk of Dementia in older adults.

Dr Hamid Sohrabi:

So, I’m involved in several projects, including the AU-ARROW, which is a sub study affiliated with WW FINGERS study that [inaudible 00:04:37], I guess, is a very well-known study worldwide. I’m involved in those studies and mainly, I’m leading the neurocognitive and outcome measures for that project.

Dr Rik Ossenkoppele:

Right. Can you give any examples of those lifestyle factors you are investigating?

Dr Hamid Sohrabi:

So, there are so many of them. There was a paper published in Lancet in 2020 coming up with about 12 different risk factors discussing that about 40% of Dementia risk can potentially be modified or changed over time if we do intervene.

Dr Hamid Sohrabi:

And the risk factors that we decided to pick up for our own study includes mainly diet, physical exercise, cognitive training, and exercise, as well as sleep. And we are also looking closely at different modes of physical exercise to see which one can be the best one that potentially can delay the risk of Alzheimer’s.

Dr Hamid Sohrabi:

Also, we are looking into psychological factors, but we are not doing any intervention. We are using observational measures just to assess and follow up on the potential for depression, for anxiety and stress, and see if the change in these can be achieved or will be achieved during the multimodal intervention that we are doing.

Dr Hamid Sohrabi:

And potentially, this intervention could be improving the quality of life of our older adults, minimizing depression and anxiety and stress level, and hopefully delaying the risk of Dementia.

Dr Rik Ossenkoppele:

Right. So, you indeed mentioned quite a list of potential interventions. Do you have a personal hierarchy of which you think are potentially most promising as a unimodal intervention?

Dr Hamid Sohrabi:

Yeah. I think the core intervention should be considered based on what are the circumstances and lifestyle factors that a person is most vulnerable to. I think a more personalized approach to lifestyle factors could be the best approach.

Dr Hamid Sohrabi:

If we, for example, come up with a package of sleep, physical exercise, diet and saying that everybody can benefit from them… Well, there are some older adults who are actually physically active, who have a great diet and follow very healthy diet.

Dr Hamid Sohrabi:

They also don’t see much of trouble with sleeping, but there are other risk factors that we should look at. For example, they may be drinking. And we know that alcohol in late life could be a very dangerous factor for developing Alzheimer’s later.

Dr Hamid Sohrabi:

The same is with potential signs and symptoms of depression, anxiety, also using or abusing different drugs, which isn’t uncommon in older adults. So, we need to go towards personalized approach for such risk factors.

Dr Hamid Sohrabi:

But the package that all studies currently are looking at includes the main physical exercise diet, and also cognitive exercises. And our sleep is in addition to this pack, which hasn’t been quite examined as part of a multimodal approach.

Dr Rik Ossenkoppele:

Right. Yeah. I really like your perspective on a more individualized approach because you can imagine someone that’s already running a marathon on a weekly basis wouldn’t benefit much from additional physical exercise, right?

Dr Hamid Sohrabi:

No. I was just going to say that we have the inclusion criteria, and many older adults that come to join our study do not meet the criteria because they’re too fit to be in this study. But they’re still very concerned about developing Dementia, and those concerns should be taken seriously. And we need to look into each individual, and what are their concerns, and why they are concerned, and then try to help them based on that.

Dr Rik Ossenkoppele:

Right. So, it’s sufficient when applying this intervention to individuals to actually prevent Alzheimer’s from emerging, so preventing the pathology from starting and/or do you think it will help individuals to better cope with Alzheimer’s Disease pathology when it happens?

Dr Hamid Sohrabi:

Well, it depends. We are considering which of these risk factors. For example, talking about sleep, we used to believe that the neurodegenerative changes that happen in the brain increase the signs and symptoms of poor sleep.

Dr Hamid Sohrabi:

But later on, we realized that in fact, sleep is a major factor in helping us to get clearance of amyloid beta from the brain, and that was supported in several CSF studies during sleep.

Dr Hamid Sohrabi:

And so, it’s two-way interaction between these risk factors and the neuro degeneration that happens as we age in some specific group of individuals who may have some susceptibility due to their genetic background, developmental conditions, and anything else that might have affected their physical health in life. Yeah.

Dr Rik Ossenkoppele:

Right. Yeah. It’s very interesting. So, one thought I had while listening to you is in general, I think it’s very difficult to change behavior. So, my question to you is also, to what degree do you practice what you preach? Do you adhere to the lifestyle advice that are generally recommended?

Dr Hamid Sohrabi:

Yeah, that’s a very good question. Change in behavior is indeed very difficult. We couldn’t just simply advise everybody go and do half an hour or 40 minutes or one hour of physical exercise a day, half an hour of cognitive training a day, and also follow a very healthy diet that may not be as enjoyable as everybody likes it.

Dr Hamid Sohrabi:

And so, combining all of these requires an effortful exercise, and each person has to put quite a bit time and energy behind it to get such intervention going. But in terms of research, usually we have things in place to promote the intervention and keep motivating our participants.

Dr Hamid Sohrabi:

For example, we have diaries that our participants in control and also in intervention groups have to complete saying that how much they have actually filed. Although this is not a direct motivation, a direct request, it implies that, “Okay, somebody’s watching me, how much I’m doing, what I need to do.”

Dr Hamid Sohrabi:

And so, people usually tend to follow the intervention because they are required to record. They also have followed up phone calls on a monthly basis. And in addition to that, we have group sessions for both intervention individuals or individual group and also control group.

Dr Hamid Sohrabi:

So, they come to group sessions, and we discuss what are the problems with following the intervention that we want them to follow, and also how we can help them to overcome those. So, these sorts of exercises can help them continue their motivation for the duration of the study.

Dr Hamid Sohrabi:

But of course, when it comes to a person that wants to get their risk factors under control, getting motivated and continuing for a long time of one, two, three, four years doing all of these different interventions require quite a bit of effort. And their psychological intervention could be one of the potentials helps that these individuals can get.

Dr Rik Ossenkoppele:

Right. And regarding my second part is the question, the bit more personal component. So, do you tick all the boxes yourself, in terms of lifestyle? So, do you get enough sleep? Do you exercise enough? Do you follow a healthy diet, et cetera?

Dr Hamid Sohrabi:

That’s a tricky one. So, I do some of it, but not all of it. Sleep is perhaps my main difficulty. Most of the work is done at night, like you and anybody else.

Dr Rik Ossenkoppele:

I recognize that very much, yeah.

Dr Hamid Sohrabi:

So, the sleep part is not as good as it should be. But the diet and, I guess, exercise is something that I’m following to some degree.

Dr Rik Ossenkoppele:

Good. Excellent. So now no more general towards the field of reserve, resilience, protective factors. So, what do you consider the hot topics in that field at the moment?

Dr Hamid Sohrabi:

Yeah. So cognitive reserve and resilience is a hard topic by itself, to be fair. I can say that there are many hot topics in this field. Right now, for example, understanding that how and what are the underlying mechanism of reserve is a very major field of study.

Dr Hamid Sohrabi:

Also, we are looking at big data, combining various studies to come up with large number of data that we can potentially look into and find out how reserve and resilience contribute to delaying or preventing Alzheimer’s Disease and Dementia.

Dr Hamid Sohrabi:

And then one of the other hot topics is developing novel composite and PACC scores. And by PACC, I mean the Preclinical Alzheimer Cognitive Composite scores so that they are independent of the measures and therefore, anybody can use it. Rather than just using specific measure for every study, people can use measures that are cognitive domain specific.

Dr Hamid Sohrabi:

And then we can hopefully come up with some understanding that these composite measures can or cannot help us to identify those who are at risk and can use these PACC scores for outcome measures of different research projects, and also for following up the treatment and intervention effect on cognitive trajectory.

Dr Hamid Sohrabi:

So, these are different hard topics that I think are of interest. But also, in relation to reserve and resilience, I think developmental approach that our current team within the reserve and resilience is looking into, and how neurodevelopmental disorders can potentially contribute to higher risk of Dementia in the presence of reserve is a very hard topic and also extremely novel that hasn’t been touched.

Dr Hamid Sohrabi:

So hopefully, we can come up with a publication soon. It is a work in progress still in the very early stages, but we are working to see if neurodevelopmental conditions like Autism, Down Syndrome, ADHD and so on, they increase the risk of Alzheimer’s. And what is the role of reserve and resilience in between.

Dr Rik Ossenkoppele:

Right. So that would point towards a very early life vulnerability that increases your risk of Alzheimer disease or Dementia in general, in later life? Did I understand that correctly?

Dr Hamid Sohrabi:

That’s correct. The problem with neurodevelopmental conditions is that they have most of those modifiable risk factors as part of the package of signs and symptoms that they have.

Dr Hamid Sohrabi:

For example, when we are talking about Autism, it comes with sleep difficulties. It also comes with social isolation. It also comes with hearing difficulties and diet problems. And we know that all of these are risk factors for future Dementia. We don’t know, however, how in the context of Autism, they work though.

Dr Hamid Sohrabi:

And also, whether autistic individuals with higher cognitive reserve, for example, will be more immune to these risk factors compared to other autistic individuals. So, these are things that we are currently trying to understand and doing research on. As I said, it is still in the very early stages, but we are very hopeful that we can come up with a review or a white paper towards early next year for publication by our PIA.

Dr Rik Ossenkoppele:

Yeah, it sounds really exciting. I already look forward to reading it. I also had two follow up questions on other hot topics you identified. So, the first one was underlying mechanisms. So, do you think that’s important for better understanding how potential non- [inaudible 00:20:05] interventions might work? Or do you think there’s also potential for maybe identifying some biological targets to boost resilience or reserve?

Dr Hamid Sohrabi:

Exactly. We think that there could be some biological underpinning to this. And that’s where some animal studies are right now conducted to identify that how potentially reserve in animals can be assessed and how those with bitter life experiences at a younger age can be more immune to neuropathology later in life compared to other animals.

Dr Hamid Sohrabi:

So, there are different projects in this from cell model to animal models. And I think that hopefully we can hear from them, not too far. In maybe a few years or even maybe sooner, we can hear the outcomes of those studies and see what they have found and how they believe reserve can contribute to the risk of Dementia.

Dr Rik Ossenkoppele:

Right. So, you mentioned the immune system as a potential player in providing resilience. Are there any other biological mechanisms that you think may be important for resilience and reserve?

Dr Hamid Sohrabi:

Well, there are many pathways. One of the main pathways that, right now, neuro imaging studies are trying to understand goes back to the function of the brain. And it seems that reserve has some functional component into it that can be imaged.

Dr Hamid Sohrabi:

We know that brain function can be imaged. That’s something that has been established. We know that the default network, for example, of the brain has been properly identified. But we don’t know how reserve could potentially contribute to all of these, or how they can contribute to reserve, the other way around. So, all of these are topics of research and hopefully, we can hear about them more in the future.

Dr Rik Ossenkoppele:

Right. Another question relates to the big data you mentioned, which indeed offers massive opportunities. So, I was just wondering in your specific field, what kind of questions will you be able to answer using big data that was not possible before?

Dr Hamid Sohrabi:

Well, that’s a very good question. Right now, we don’t have big data. We are trying to go towards that, end up accessing big data. So that means that several large-scale studies that have been completed or are still undergoing are coming together, helping each other and using databases that can be combined.

Dr Hamid Sohrabi:

We are trying to understand that with such big data, can still reserve be considered as one of the factors that contribute to the risk of Dementia? And also, as you can imagine, the cohort composition for each of these studies is different.

Dr Hamid Sohrabi:

Some studies have different ethnocultural groups within them. Some studies don’t have, and they’re maybe Caucasian-based cohorts. Some studies have different lifestyle factors involved in, compared to others.

Dr Hamid Sohrabi:

And all of these can be potentially looked at when we combine all the data together, because then that gives us a continuum of data that we can go from 0 to 100 understanding better that which factor and in between how reserve could contribute to the future risk of Dementia.

Dr Hamid Sohrabi:

One of the other potentials is that big data can help us to look into genetic backgrounds, and how genetic risk factors and reserve can interact to increase or decrease the risk of Dementia later in life. So, this isn’t something which is quite established right now. We are hoping that with big data, we can have a better answer to such questions.

Dr Rik Ossenkoppele:

Yeah. Thanks so much. It’s very clear. I think it will be a challenging question as well because there are so many publications in the field. But I’m going to ask you to pick the one publication from last year that you are most excited about from your field, and please explain why.

Dr Hamid Sohrabi:

One publication that I’m most excited? So, I should say that the publication that I’m very excited about is a paper published by Yaakov Stern and colleagues. And that paper is a white paper describing how reserve should be defined, how it should be studied, and how it should be measured.

Dr Hamid Sohrabi:

I think that paper provides a framework for all of us to talk the same language. And that’s where my excitement comes because if you look at the papers in our field, you see that each researcher has come up with their own definition of reserve, and resilience, and also maintenance and so on. Brain maintenance and so on.

Dr Hamid Sohrabi:

And so, this paper gives that framework that if you are talking about reserve, everybody knows what we are talking about. And if you are talking about measures for reserve, everybody again uses similar measures so that we know what we are measuring. That kind of framework, I think, can help us a lot in future studies.

Dr Rik Ossenkoppele:

Right. Yeah. So that relates to my next question is, so what you consider as the major challenges in the field. So, one major challenge is, of course, making sure people talk the same language, right? If they say reserve, that they’re actually meaning the same thing. Are there any additional challenges in the field at the moment?

Dr Hamid Sohrabi:

Well, there are many challenges. Like any other field of research, our field is not without challenge. Of course, identifying proper channels of funding is [inaudible 00:27:32]. We know how getting funding is difficult and when it comes to reserve, it becomes even more difficult.

Dr Rik Ossenkoppele:

Is it more difficult, do you think…? Because that’s important information for the early career researchers that are listening right now. So, is this field, is it more difficult to obtain funding?

Dr Hamid Sohrabi:

I’m a bit biased though, I should say, because that’s my field. And so, I think that our funding is very tight and very, very limited. For early career and mid-career researchers, there are many pathways that definitely they can tap into when it comes to reserve.

Dr Hamid Sohrabi:

And one of the initiatives, I think it was NIH or NIA, that Yaakov Stern and colleagues promoted was to get support for early to mid-career researchers so that they can get funding to specifically go and do research on reserve. So, although I’m biased, I think we all are trying to get more funding and definitely, it’s not an easy job.

Dr Rik Ossenkoppele:

We can agree on that, I guess. Irrespective of the field we’re working on.

Dr Hamid Sohrabi:

Yeah, exactly.

Dr Rik Ossenkoppele:

All right. So, can you tell us a little bit about how the work of the reserve, resilience and protective factors Professional Interest Area supports your field of research?

Dr Hamid Sohrabi:

Yeah. I guess one of the main reasons for such PI is to promote collaboration between researchers, and also to come up with novel ideas, and to develop consensus amongst researchers.

Dr Hamid Sohrabi:

And so, our PI has been pretty successful in doing that with webinars, with scientific sessions, also white papers. And the main white paper that came just a couple of years ago by our PI and many other initiatives that can help our field to move forward.

Dr Hamid Sohrabi:

So, I guess for the early to mid-career researchers, it is pretty important to know that they can find many information and many details about what our PI is doing and how our PI is working in the webpage within the Alzheimer’s Association ISTAART, and also through the LinkedIn page that we have for our reserve and resilience and protective factors.

Dr Hamid Sohrabi:

So, the other initiative that our PI has been doing to promote our research is they’re trying to establish a… Well, not to establish but they’re trying to come up with a newsletter right after AIC.

Dr Hamid Sohrabi:

So that newsletter will be, hopefully, providing an oversight of all the reserve and resilience-related research that have been discussed within the AIC or has been presented as oral or poster presentations.

Dr Hamid Sohrabi:

And that could provide a good glimpse of what everybody is doing in this field. And definitely, can be a supportive pathway for early to mid-career researchers to find out about novel research projects that are going up.

Dr Rik Ossenkoppele:

Right. Lots of activities. That’s good to hear.

Dr Hamid Sohrabi:

Exactly.

Dr Rik Ossenkoppele:

So how does the executive committee look like at the moment? Who are the members?

Dr Hamid Sohrabi:

Yeah. Well, we have quite a good number of early, mid, and senior researchers. We have David Bartrés-Faz, who’s a professor of neuroscience, as our chair. We have an assistant professor, Eider Arenaza-Urquijo, as our vice chair. We have Dr. Samantha Loi as our program chair, and communication chair is Elisa De Paula Resende.

Dr Hamid Sohrabi:

Also, we have three sitting committee members, including Nicolai Franzmeier, Jet Vonk, and myself. And we have two student representatives, Harriet Demnitz-King and also Stephanie Schultz.

Dr Hamid Sohrabi:

And there is our immediate past chair, Dr. Prashanthi Vemuri who’s also helping us to have a continuation of what has been previously achieved to know and hopefully, to the next group of researchers who will be taking over.

Dr Rik Ossenkoppele:

Right. And for any early career researchers that may be listening to this podcast right now and got, like me, very fascinated by everything you are telling about this field and the PI in particular. So, if they would like to be involved in the PI, are there any possibilities for that?

Dr Hamid Sohrabi:

Sure. It’s an extremely easy job. Our PI is one of the very easygoing and most welcoming PIs, I should say. Again, I’m biased but there are different pathways for that. One pathway is just becoming a member of ISTAART and through that, then you can choose the PIs, including our PI.

Dr Hamid Sohrabi:

And you can then get involved in different activities, from collaborations, to networking, to papers that are currently under development and also in potential grant applications and every other activity that are going on.

Dr Hamid Sohrabi:

You can also join our LinkedIn page and through that, you can get updates about everything that our PI is doing. And again, you can communicate with other members of the PI and get to hear from them or start collaborating with them.

Dr Hamid Sohrabi:

So, these are the main two pathways that you can get involved in our PI. But as I said, our PI is pretty welcoming and everybody, early, mid, or senior researchers are most welcome to join in and contribute to our PI.

Dr Rik Ossenkoppele:

So, are there any activities planned for the next year or maybe years?

Dr Hamid Sohrabi:

Yes. There are many activities, indeed. As I mentioned, the review paper on neurodevelopmental disorders and reserve. Also, we are having some of our PI members working closely on how and what the role of gender and sex reserve is.

Dr Hamid Sohrabi:

And also, how ethnocultural different groups can have different reserve potentials, and what does that mean, in terms and in relation to Alzheimer’s Disease and Dementia? So, these projects are ongoing. And again, as I mentioned, we welcome anybody who wants to join in and help us with the progression of these projects.

Dr Rik Ossenkoppele:

Are you planning to go to AIC yourself this year?

Dr Hamid Sohrabi:

Yeah. Well, I was planning, and I was hoping, and I’m still hoping. But as you can imagine, it all depends on the permission and support of university due to the COVID-19 pandemic. And so, from Australia to the US, it’s quite a bit of way, and so the flights are pretty long usually, and that requires permission from university because of all the insurance-related consequences and so on. So, if I get the permission, then I’ll be delighted to go and attend in person.

Dr Rik Ossenkoppele:

Right. And are you presenting anything?

Dr Hamid Sohrabi:

No, I’m not this year. My data and also my results were not ready to be presented. Hopefully for next year I’ll be presenting, but one of my postdocs is presenting.

Dr Rik Ossenkoppele:

That’s always good. So many thanks. So, it’s time to end today’s podcast recording, but before we go, I do have a final question. So, what advice would you give to any aspiring Dementia researchers out there who are thinking of looking into Dementia?

Dr Hamid Sohrabi:

Yeah. Dementia research is pretty interesting and also, it has huge translational value into the life of other individuals. So, no matter what kind of research you’re interested in, as long as it’s related to Dementia and specifically Alzheimer’s Disease, I’m sure that your path will help somebody in future.

Dr Hamid Sohrabi:

There are, of course, some potential difficulties, like any other field of research. But what I usually tell my postdocs and also my students are that if you work hard before submitting anything, which is usually a grant application or a paper, then definitely you don’t need to resubmit it.

Dr Hamid Sohrabi:

So that means that spend enough time, don’t rush into submitting a manuscript or submitting a grant application when they’re not ready. Work on it. Even if it takes two years, it’s better than just keep repeating yourself and resubmitting without success.

Dr Hamid Sohrabi:

So, I usually encourage everybody to work hard before going for any submission. And I guess that that could be something that our early to mid-career researchers can also consider.

Dr Rik Ossenkoppele:

Yeah, that is some very solid advice. So many thanks to you, Hamid, for taking the time to join us today. And it was a pleasure talking with you.

Dr Hamid Sohrabi:

No problem at all and thank you for having me.

Voice Over:

Thank you for listening. You’ll find profiles on today’s panelists and information on how to become involved in ISTAART on our website at dementiaresearcher.nihr.ac.uk, and also at als.org/istaart.

Voice Over:

We’ll be back tomorrow with the next recording in our ISTAART PIA Relay Podcast series. Finally, please remember to like, subscribe, and leave a review of this podcast through your website, iTunes, Spotify, SoundCloud, and in all the other places you find your podcasts. Thank you.

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