Scott Sperling
Welcome to Meet the Authors, a podcast brought to you by a collaboration of the Society for Clinical Neuropsychology and the journal 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 early career leader, Dr. Zachary Resche, will be discussing an exciting paper entitled ‘The Signs and Symptoms Method in Neuropsychology, a standardized observational examination of cognitive functions can be effective in detecting mild cognitive impairment’. We’ll be discussing this paper with two of the authors, Dr. Carlo Abbate and Dr. Alessia Gallucci. I’d like to now introduce our early career leader and esteemed guests. Dr. Resch is a life span neuropsychologist at NYU Langone Health and Bellevue Hospital, who specializes in the care of patients with epilepsy.

He completed his Ph.D. in clinical psychology at Rosalind Franklin University of Medicine and Science, his pre-doctoral internship at the James A Haley Veterans Hospital, and Postdoctoral Fellowship in Clinical Neuropsychology at the University of Illinois at Chicago College of Medicine. Dr. Resch served as the chair of the Society for Clinical Neuropsychology’s Association of Neuropsychology, Students and Trainees, or ANTS, and as their delegate for the Minnesota 2022 Conference to update the education and training guidelines in clinical Neuropsychology.

Welcome, Dr. Resch. Dr. Abbate earned his doctorate in Pathophysiology of Aging from the University of Milan. He’s a senior clinical neuropsychologist and researcher at the IRCCS Fondazione Don Carlo Gnocchi, Istituto Palazzolo in Milan, and senior editor for the Journal of Alzheimer’s Disease. Dr. Abbate’s research focuses on the novel methods of detecting the early symptoms of cognitive decline and dementia. And our other esteemed guest, Dr. Gallucci, earned her doctoral degree in neuroscience from the University of Milano, Bianco.

She is a principal investigator of a research unit at the Fondazione Don Carlo Gnocchi in Milan and a teaching assistant of the Principal and Practice in clinical research Program in the Harvard School of Public Health. She leads clinical research aimed at identifying early cognitive and neuropsychological markers of dementia and its prodromal forms using new technologies and artificial intelligence.

She’s also engaged in projects aimed at improving care models for people with cognitive impairment and dementia. So welcome, doctors Abbate and Gallucci.

I’ll now turn our discussion over to Dr. Resch.

Zachary Resch
All right. In their paper, the authors examine the diagnostic sensitivity and specificity of what they term the NeuroPsychological Examination, or NPE, which is a systematic method of collecting and quantifying cognitive and behavioral symptoms during a clinical interview. For those who may not have yet read your paper, can you briefly summarize the main findings of your study?

Alessia Gallucci
Yeah, sure, I can start. So first of all, it is important to say that our group developed a new diagnostic procedure for a cognitive impairment called NeuroPsychological Examination, or NPE, to be administered before the testing session. This meter consists of a semi-structured interview investigating the patient’s cognitive functionality based on a pre-established list of signs and symptoms of cognitive dysfunction relating to different cognitive domains and data will be presented better later by my colleague, Dr. Abbate.

Interestingly, this method showed promising preliminary results in terms of diagnostic sensitivity in cases of both dementia and MCI. Indeed, in one of our previous, retrospective study that we published in 2022, we decided to retrieve the NPE of patients with Alzheimer’s dementia and vascular dementia and healthy controls. And what we found was that the number of signs of both the two clinical groups were far higher than the group of healthy controls.

Moreover, what we found was that the NPE was also sensible in differentiating between Alzheimer’s dementia and vascular dementia. Similarly, in the paper we published in 2022 in Neuropsychology, we registered a significantly higher number of signs in patients with an MCI or dementia than in control group of people with subjective cognitive decline. And in this latter study, we also found differences in the number of signs between amnestic and non-amnestic MCI patients.

So as will present my colleague, Dr. Abbate, these methods showed high sensitivity in collecting data from dementia patients and MCI patients. So I will leave the word to my colleague.

Zachary Resch
Okay. I guess the first question then, based on your study, is what is the practical strategy for completing the NeuroPsychological Examination? So, for example, are symptoms documented as they emerge during the clinical interview or is the NPE intended to be completed following the interview based on recollection?

Carlo Abbate
Essentially, we observe the patient’s behavior while he or she is doing the interview and promptly detect and note signs of cognitive dysfunctions as they emerge. It is an observation, so I will say naturalistic, etiological Laurence, like in the visit to the psychologist situation. Actually the observation starts even before the interview, when the patient enters the room, introduces himself to the psychologist, lays down the coat, sits in the chair, shows the clinical documentation. As soon as the patient enters the assessment room, the NPE begins.

Zachary Resch
So it sounds like the NPE might be designed to supplement the standard clinical interview, which might vary by clinician. Or do you intend to have it function more as a standalone interview and behavioral examination method?

Carlo Abbate
Most certainly the NPE is that of a standalone method with a specific structure. There is a well-defined list of signs. There is a set number of cognitive domain or dysfunctions to be examined. There is an interview outline, a common setting, which is the neuropsychologist’s visit room, and also writing time, that should not exceed 30 minutes. However, there is also a strong degree of freedom in the examination.

The setting obviously involves differences and the interview questions could be expanded and their order changed. At the same time, the questions can be also adapted based on the different characteristics of patients.

Zachary Resch
So it sounds like a semi-structured interview, but with very specific behavioral examination methodology. How might common co-occurring conditions such as sleep disturbance or depression impact cut off scores that discriminate between subjective cognitive impairment and MCI?

Alessia Gallucci
Certainly. If a co-occurring condition can affect a cognitive function, then it can affect the outcome of the NPE and the discrimination between subjective cognitive decline and MCI. But this is the case if we consider just this sum, though the total sum of pathological signs that emerge in each condition, such as control group, MCI, or dementia patients, regardless of the cognitive domain or the kind of signs, emerge.

However, what we found in our works was that although patients with vascular dementia and those with Alzheimer’s dementia had the same number of signs in the NPE, vascular dementia had more pathological signs in psychomotor slowness in our findings, whereas the Alzheimer’s dementia had more signs in temporal and spatial disorientation, apathy and anterograde memory. Similarly, in the last paper we published, we observed that amnestic and non-amnestic MCI had the same number of signs, of course, but amnestic MCI had more signs on anterograde memory and spatial and temporal orientation and non-amnestic MCI more signs in selective attention.

And of course, based on these findings, we can also say that the NPE retains a high diagnostic sensitivity even in the presence of comorbidities. As I said before, because we might be able to bring onsets of signs that are specific to each comorbid condition.

Zachary Resch
Sounds like the NPE has a lot of potential, even on like a more item-specific level for differentiating between different degenerative conditions or even some of the comorbidities that might be impacting the score. How do you see the NPE advancing current neuropsychological practice given its sensitivity and specificity for detecting patients with MCI in this study and for differentiating between AD and vascular dementia in your prior research?

So, for example, given the long wait list for neuropsychological evaluations in many clinics, could the NPE be used to help determine who needs a full neuropsychological evaluation, or is there incremental value in conducting neuropsychological testing given the validity of the NPE?

Carlo Abbate
Well, I start saying that I am not a fan of brief screening in neuropsychology. To this regard, I wrote a previous very critical article on the risks of the two-step strategy in the diagnosis of MCI. You cannot study the cognitive system and this disorder in a few minutes as cognitive faculties are measured in behavior and behavior takes up time.

The unit of measurement of behavior is at least of tens of minutes, not few minutes or seconds. I believe that neuropsychology works if it is done in the time of neuropsychology. We have to fight against this obsession with few minutes in neuropsychology. That said, the NPE is not meant to be a substitute for testing, but is one of the tools that is part of the neuropsychologist assessment background, along with history taking, interview with the patients about the subjective cognitive symptoms and testing.

Not only that, but the testing sessions is also an extraordinary situation for many pathological signs to emerge. In some cases, it’s better than the interview. Some signs, you know, are measured only at testing, for example, closing in and drawing, stuck in set perseverations, confabulation, the memory tests – everyone knows them: they were the so-called qualitative data. In fact, the second part of our ongoing project involves performing the NPE during testing.

At this point, I will say that the NPE plus perhaps a screen test such as the mini mental state examination or the Montreal Cognitive Assessment, may be sufficient to rule out suspicion of dementia. So they could be a possible preliminary test while waiting to perform an extended evaluation. Otherwise, NPE is not sufficient to exclude the suspicion of MCI. At the same time, I think that the NPE might help neuropsychologists have a greater impact on health care and receiving more referrals.

Indeed, NPE can always be done. It is quick and inexpensive, and can be repeated without learning effects.

Zachary Resch
Sounds like there’s a lot of potential for use of the NPE, that’s for certain. I’ll look forward to seeing how it can be applied to testing. So the NPE is a systematic way of quantifying information and observations obtained during a clinical interview, which we often conduct prior to our neuropsychological testing, and then used to inform diagnostic impressions.

As such, what are the specific benefits of quantifying the clinical interview, and is there evidence that the NPE is superior in differentiating subjective cognitive decline, MCI and dementia compared to a well-conducted clinical interview?

Carlo Abbate
I believe that the NPE and a well-conducted clinical interview are the same thing. Experienced neuropsychologists are good observers and during the interview they certainly already pick up all the signs we picked up in the NPE, maybe even more than us. Look, probably Luria detecting more signs than us. In fact, neuropsychologists already do the NPE. We didn’t invent anything. So I don’t know if the NPE is better than a classical interview in discriminating between subjective cognitive decline and MCI and dementia.

But certainly there are advantages of making this complex procedure standard. There are advantages to quantifying the clinical interview. If you don’t know the signs well, you won’t see them. Having a list with a wide, pre-established set of signs at hand helps you keep them well in mind when you serve. Introduce guest signs, graduations helps you quantify them better.

So having a quantitative report of signs helps you evaluate effectiveness and make comparisons of repeated visits of the same patients or comparison between different diseases. It helps also to communicate between neuropsychologists about results. And it helps surely to teach young neuropsychologists. In a word: standardizing helps to do science. Neuropsychologists are scientists, we have entered health systems, we have entered medicine.

But evidence-based medicine requires quantitative data, no more informal examinations and qualitative data. Also, we must adopt the clinical method of neurology of medicine that is based on detection of signs and symptoms. My dream is that worldwide neuropsychologists perform the same preliminary examination, just as all neurologists do the same neurological examination.

And the same time, the cognitive system is always the same in all human beings. The signs of cognitive dysfunction do not change. They change probably with the type of disease, but they are not different between people living in Boston or Milan. I’m tired of worrying about the Canadian battery, Australian battery, Spanish battery, French battery and so on.

Zachary Resch
Yeah, that makes sense. I think it would be good to standardize our methodology even just beyond the testing. So having a behavioral examination method for quantifying some of this would be good, especially for young trainees as they’re learning to do these interviews and conduct in such a way. Could the NPE be effectively administered by non-neuropsychologists? And what would the training for neuropsychologists or other clinicians interested in using the NPE entail?

Carlo Abbate
In our idea, the NPE is what the neurological examinations is for neurologists: a standard preliminary examination of cognitive functions. As such, the NPE is not just, let’s say, a tool, of which you just need to learn the administration rules. But it is like the expressions of our profession. You need behavioral observation skills of the etiological type, knowledge about the cognitive system and cognitive dysfunction signs, the ability of detecting these signs promptly when they occur.

Neuropsychologists are the experts of the cognitive system and its dysfunctions. I don’t see how other professionals can have this expertise. Certainly we can teach our examination to other professionals, as other physicians do, with the neurological examinations. Yes, but if you read the medical record of a patient with Parkinson’s, multiple sclerosis, epilepsy, do you look at the neurological examination wrote by a neurologist or that wrote, for example, by a cardiologist?

Zachary Resch
Yeah, that makes sense.

Alessia Gallucci
If I can add something, I would say that this is maybe the most important lead of our method of the NPE, because it is based on the knowledge of a senior clinician and on the knowledge about specific skills in detecting signs and symptoms and also to connect the sign that the clinician is able to find out in the patient behavior with the cognitive domain that the sign is related to.

So this is the main limitation, but also the potential, I think because is something that is not like a just formal or a fast evaluation, but is evaluation that is based on specific skills and capabilities. And if I can report something based on my personal experience, many times what happened to me was that I did not catch the sign while taking the exam that were essentially seen or pointed out by the senior clinician. Or other times,

I was unable to get the sign while I was writing down or thinking about the question to ask to the patient, but maybe I check them later on during the interview. Or other times, although I noticed a behavior, I did not recognize it as a relevant sign, so I was not able to connect the sign to the cognitive domain. For instance, certain ways of presenting clinical documentation are sitting on the chair by the patient in the interview setting. So this is the main limitation, but also the potential of this instrument, I think.

Zachary Resch
Certainly relies on a lot of expertise then, and clinical decision-making.

Alessia Gallucci
Yeah, exactly.

Zachary Resch
All right. Well, I’d like to thank you both for discussing your study and sharing your expertise in this important area of research. I will now turn it back over to our host, Dr. Sperling.

Scott Sperling
And I’d just like to echo those sentiments, really. On behalf of the Society for Clinical Neuropsychology and the journal Neuropsychology, really extend my gratitude both to Dr. Resche for this wonderful interview and appreciations for doctors Abbate and Gallucci for taking the time to discuss this excellent study. And I’ll say as somebody who tends to preach about some of our forefathers and mothers of cognitive neuroscience and behavioral neurology and neuropsychology thinking squarely of Luria and others that somehow seem to get missed sometimes in sort of modern day teaching, you know, really thinking about the importance of behavior and thinking really closely about behavioral markers of cognitive dysfunction and what that can teach us in terms of diagnostics and differential. So your work here is very well taken. So I certainly appreciate your expertise and the time that you spent with us today. Thank you, and take care.

[Abbate & Gallucci] Thank you very much.