Scott Sperling
Welcome to Meet the Authors, a podcast brought to you by a collaboration of the Society for Clinical Neuropsychology and the Journal of Neuropsychology. My name is Dr. Scott Sperling, and I’m grateful to be your host. In this podcast, student leaders in neuropsychology will discuss prominent, recently published studies with the authors who undertook the research, allowing for a behind-the-scenes look into the development, implementation, analysis and future implications of cutting edge neuropsychology research.

Today, our student leader, Dr. Kritika Nayar, will be discussing an exciting paper entitled Cross-sectional associations of CSF tau levels with Rey’s AVLT: A recency ratio study with the paper’s author, Dr. Davide Bruno. I’d like to now introduce our student leader and esteemed guest. Dr. Kritika Nayar is a pediatric neuropsychology and autism research postdoctoral fellow at Rush University Medical Center.

She completed her doctoral degree in clinical psychology and Master’s degree in biostatistics from Northwestern University and her pre-doctoral Pediatric Neuropsychology internship at Texas Children’s Hospital Baylor College of Medicine. Her research is focused on disentangling mechanistic, neurocognitive underpinnings of social differences in autism. Welcome, Dr. Kritika Nayar. Dr. Davide Bruno completed his doctoral degree in cognitive psychology from Keele University.

He has worked at the University of Southampton, the University of Massachusetts, Amherst and New York University. He is currently a Reader in Psychology at Liverpool John Moores University in the UK. Dr. Bruno’s research is in memory and dementia, including the development of cost effective memory based tools for the early identification of neurodegenerative pathologies. Welcome, Dr. Bruno. Thank you very much.

I’ll now turn our discussion over to Dr. Nayar. [Kritika Nayar:] Thank you so much, Dr. Sperling, for that introduction. I’m really excited to be here to be able to discuss your paper, Dr. Bruno. A brief introduction: in their paper, the authors examined and compared the associations between traditional memory scores from the Rey Auditory Verbal Learning Test, or RayValt, and a novel process based score of memory and CSF biomarkers of Alzheimer’s disease.

Kritika Nayar
So for those who may not have yet read your paper, can you briefly summarize the main findings of your study, please? [Davide Bruno:] Sure, Kritika. Thanks a lot, by the way, for having me talk here. So what we wanted to do was test out some alternative ways of scoring the AVLT, which we have done in the past. And in this case we wanted to look at how these alternative ways associated with CSF biomarkers of Alzheimer’s disease.

Davide Bruno
And we wanted to follow the ATN classification. So one for amyloid, one for total pathological tau, one for neurodegeneration in terms of CSF. And we are generally interested, whenever possible, and try and find ways where we can have accurate tools in neuropsychology, but also tools that are quite cost effective and easy to administer, easy to use.

So we didn’t want to reinvent anything. We wanted to use something that is commonly used already, like the AVLT, which is quite popular to use, and just extract new metrics without too much of an extra effort. So what we’ve looked at here specifically is a measure called the recency ratio. So as many people will probably be familiar with, there is such a thing as the serial position effect dating back at least the late 1800s in terms of research.

So if you study something, if you study a list of words, if you study a list of items, you’ll find that you’ll remember things that were learned at the beginning and at the end of the list, much better than what you learned in the middle. So this will give you a memory curve where basically you perform better at the extremes.

And this is especially true when you’re looking at memory, which is tested immediately after learning something. And the application of your position to Alzheimer’s disease and related dementias is not new either – from before my time for sure. In fact, a paper from ‘95 by the Carlesimo team kind of sparked my interest in recency specifically because what they showed very well graphically, I guess, is that when you take a person with Alzheimer’s disease, they tend to have relatively good preserved recency memory.

So memory for recent items on the list when tested immediately after the presentation of the list. But then after a delay, they lose it. So I thought, well, maybe you can leverage this drop in recency performance and you can use this drop, you can use this gap difference as a tool. And that’s where I guess the recency ratio comes from, where we basically just calculate a ratio between recency performance immediately after learning something and recency performance after a delay.

So in this case we applied the recency ratio as alongside traditional scoring of the AVLT to data from the Wisconsin Registry for Alzheimer’s Prevention, which is based at University of Wisconsin, Madison. We had 235 total participants. And what we found was that the recency ratio was associated better than the traditional metrics to specifically the tau biomarkers, not so much the amyloid beta 42 biomarkers, sorry I forgot to say.

Then eventually the three biomarkers that we used were amyloid beta 42, P-tau and T-tau. So there was a very good association between recency ratio in the AVLT and P- and T-tau, no association with the amyloid beta. At the same time, the association between recency ratio and tau was better than the association between the traditional metrics and tau. So in a nutshell, this is what we’ve got.

Kritika Nayar
Thank you so much, Dr. Bruno, for that summary. It really, really interestingly has some follow up questions with respect to your findings. We’d love to discuss that. So our first question is your study sample was drawn from a larger longitudinal study of primarily white, well educated, English speaking individuals. And given that there are potential differences in brain morphology across racial and ethnic groups and the importance of culturally sensitive assessments, what specific research steps are you planning to take?

Or might you suggest others take to examine the generalizability of these findings from your paper? [Davide Bruno:] I would love to be able to generalize the findings to newer populations, larger communities, different communities and so on. What I find is that it’s been really, really hard in the sense that for the most part I work with secondary data analysis. So I take data that’s already available and I really struggle to find databases that are large and are not nearly exclusively white Caucasians.

Davide Bruno
One study that I am currently in the near publication, I guess, has used the data from the Rush Alzheimer’s. So Rush University, I forget exactly which database because they have a few. And a few of those databases target specifically Latino populations in Chicago and African-Americans in Chicago. So in that specific paper, we have a few more nonwhite people, but still not a lot.

I don’t have a magic bullet for this. I don’t know exactly how to reach out to wider populations, but I know it’s very important. And I have been looking around myself trying to expand, but it’s not been easy from my perspective. One thing that I suppose could be useful is, again, sort of going back to what I was saying at the beginning.

If you have tools that are less intimidating for data collection, so if you’re not scaring people off with lumbar punctures or more expensive procedures, perhaps you may be able to recruit more, including more marginalized communities, or at least I hope so. But obviously that will take some work. [Kritika Nayar:] Absolutely. Especially when you’re thinking about that secondary data analysis and relying on those large databases that exist.

Kritika Nayar
Hopefully, things will change as we kind of continue moving forward. Dr. Bruno, do you think that a recency ratio metric on visual-based memory measures that may rely less on language would be similarly associated with Alzheimer’s disease-associated biomarkers across groups with kind of thinking about different linguistic and/or cultural backgrounds? [Davide Bruno:] That is a beautiful question, and I would like to know the answer to that question myself.

Davide Bruno
And I’m saying that because we were trying to look at visuospatial assessments as well and try to look at visuospatial assessment from a time progression standpoint. So, for instance, if you’re drawing a complex figure, where do you start drawing it from? And then how do you complete the drawing? And then does that sequence translate later on in the way you remember it?

Or analogously, if you’re doing any of those visual association tasks where you have one block of items, then a second block and so on and so forth, you could do that. However, unfortunately for the purpose of this answer and for myself, I haven’t been able to address these questions empirically. So this is a great question. Unfortunately, I have to say, ‘I don’t know’ to. […] [Kritika Nayar:] Good. Next question.

Kritika Nayar
Your results show that the recency ratio is significantly associated with P-tau and T-tau, as you had indicated, thinking that it might be a sensitive clinical measure for identifying neurodegeneration. In contrast, the recency ratio was not associated with amyloid beta 42, and given that changes in amyloid beta 42 occur prior to tau accumulation in Alzheimer’s disease, we’re curious to learn about what might explain the lack of association between the recency ratio and amyloid beta 42 in your sample.

Davide Bruno
So this is a bit speculative, but we’ve been doing a lot of work with serial position, not just with recency but also with primacy effects. So if you go back to the beginning of the list, what we tend to find is that the memory for primacy, so memory for early list items, tends to associate better with amyloid beta signal, in PET as well as postmortem, and tends to predict pathology way sooner, which makes sense because amyloid obviously begins deposition sooner before any sort of tauopathy or tau damage.

So if primacy is more in tune with amyloid deposition then it would track potential pathology later on. And why is that? I think what’s going on with primacy is that it is more sensitive to the associative areas of the brain where, for instance, you find amyloid deposition to be more significant, I suppose, than if you’re looking at medial temporal lobe and memory areas.

And we know also from other studies that associative memory is a very sensitive tool. So I think that might be one, I guess, part of the puzzle. Whereas on the other head, which is more to the point of your question, recency seems to tap more into specifically medial temporal lobe damage. So you use recency more in terms of cross-sectional here and now damage.

What’s going on right now in this person, not what’s going to happen in ten years. In fact, we were just working yesterday on some data looking at PET tau and the interial cortex and the hippocampus and so on. And we do find recency ratio to be particularly sensitive to that, but not so sensitive to other areas of the brain.

So I think particularly the loss of recency possibly due to the fact that when there is impairment, immediate recency is still preserved but that drops down, it might be signaling a failure to consolidate information because we have the information immediately. Maybe it’s just working memory, maybe it’s psychoic memory and so on. So it’s right there, but then it doesn’t stick, it’s not preserved.

So it might be a good tool to identify the failure to consolidate. But again, a lot of this is speculative because I haven’t been able to quite disentangle everything, but this is the best I can tell you right now. [Kritika Nayar:] Absolutely. Lots of next steps from your paper. And I think this actually leads really nicely to our next question. In the sample

Kritika Nayar
in your study, it was largely comprised of non cognitively impaired individuals. And so we’re curious to learn what insights do the results of your study offer in terms of the potential long term cognitive trajectories and risk of developing MCI or dementia, particularly given the lack of relationship between the recency ratio and amyloid beta 42? [Davide Bruno:] Mm hmm. So first of all, I have to say I do like taking the individuals that are cognitively unimpaired and they don’t present any clinical signs because I think if you can find some signal within that population it’s more informative because it’s basically just grabbing somebody off the street in a way they don’t seem to have any problems, but you

Davide Bruno
can do something slightly more sophisticated and whatever else you’re doing and you’ll find some potential problems. Now, it sounds grim, you know, grab somebody from the street and tell them they have a cognitive problem. But I think going back to what I was saying before, in terms of longer term prediction, you might be better served by using the early part of the list.

We have a paper that’s actually, I think has come out in a competing journal, so I won’t mention, but recently looking at story recall and loss of primacy instead of loss of recency. And we found it is quite a very good predictor of, I guess, Alzheimer’s pathology, as measured by the A-beta 42 P-tau ratio. So if you want to predict, you might want to look at the first part of the list instead of the last part of the list.

If you want to know how well a person is doing right now, you may want to concentrate on the second part of the list. So I guess that’s my current thinking, which kind of echoes what I said before. [Kritika Nayar:] Absolutely, Yes. Dr. Bruno, thank you so much for discussing your study and sharing your expertise in this important area of research.

Kritika Nayar
I know our listeners will be really interested to hear all about it, so I’m going to turn it back over to our host, Dr. Sperling. Thank you, Dr. Bruno. [Davide Bruno:] Thank you so much. [Scott Sperling:] And I’d just like to echo those same sentiments, really, on behalf of the Society for Clinical Neuropsychology and the Journal of Neuropsychology. I really want to extend my gratitude to you, Dr. Bruno,

Scott Sperling
and to you, Dr. Nayar, for your efforts in hosting this podcast and certainly Dr. Bruno for this really excellent work. And I think just your entire body of work and your aims to really be more sort of forward thinking and how we can really refine our measures and get away from sort of what’s been traditional so that we can have greater specificity in terms of our assessments, as you mentioned, both in terms of who we’re working with and that’s in front of us now.

And then, as you mentioned earlier, really critically thinking about developing better metrics for predictive reasons moving forward. We know the aging crisis, unfortunately, isn’t going anywhere all too soon. So whatever we can do to help with neuro identification is, I think, critically important. So your paper is excellent. And again, we sincerely appreciate your time and energy today. Thank you both, and take care.