The Fundamentals of Neuropsychology: Breaking Down Cognition, Memory and More

Accreditation Statement

Image

In support of improving patient care, the University of Wisconsin–Madison ICEP is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.

Credit Designation Statements

For more information about continuing education credit for this episode, visit the ICEP online learning portal at https://ce.icep.wisc.edu/dementiamatters/neuropsychology 

The accreditation for this course expires 3/25/2025. After this date, you will no longer be able to access the course or claim credit.

Claiming Credit

An ICEP account is required to claim credit and to complete the episode evaluation form. Create an account

To claim continuing education credits using the texting function:
● At the end of the podcast episode, you will receive information about texting in a code
with your cell phone.

To claim continuing education credits through the ICEP online learning portal.
● Visit https://ce.icep.wisc.edu/dementiamatters/neuropsychology. Go to the Register tab, click the Begin button and under the Course Progress section, click on Attendance Code -> Start and enter the text code given at the end of the podcast episode.

To complete the episode evaluation:
● Go to the Register tab, click the Begin button and under the Course Progress section, click on Episode Evaluation -> Start

Learning Objectives

As a result of participation in this educational activity, members of the healthcare team will:

1. Define cognition and memory.
2. Describe the cognitive domains testing in the neuropsychological evaluation.
3. Describe the limitations of cognitive testing, particularly cognitive screeners.

References/Resources

• Brain basics: Know your brain. National Institute of Neurological Disorders and Stroke. November 15, 2023. Accessed March 20, 2024. https://www.ninds.nih.gov/health-information/public-education/brain-basics/brain-basics-know-your-brain#:~:text=The%20brain%20is%20the%20most,qualities%20that%20define%20our%20humanity.
• Harvey PD. Domains of cognition and their assessment. Dialogues in Clinical Neuroscience. 2019;21(3):227-237. doi:10.31887/dcns.2019.21.3/pharvey
• Victoria Williams’s Bibliography - NCBI. National Center for Biotechnology Information. Accessed March 20, 2024. https://www.ncbi.nlm.nih.gov/myncbi/victoria.williams.1/bibliography/public/.

Transcript

Intro: I'm Dr. Nathaniel Chin, and you're listening to Dementia Matters, a podcast about Alzheimer's disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news in Alzheimer's disease research and caregiver strategies. Thanks for joining us.

Prerecorded Dr. Nathaniel Chin: This episode is approved for continuing education credits for physicians, physician assistants, nurses, and other members of the healthcare team through the Interprofessional Continuing Education Partnership at UW–Madison. At the time of this recording, Dr. Victoria Williams discloses the following relevant financial relationships with ineligible companies as a contractor: Amylyx Pharmaceuticals and Cognito Therapeutics. Information on how to claim credit will be shared at the end of this episode. Additional continuing education information is provided in the show notes.

Dr. Nathaniel Chin: Welcome back to Dementia Matters. I'm here with Dr. Victoria Williams. She is a clinical neuropsychologist whose research investigates how modifiable health and lifestyle determinants across the lifespan modify brain aging, cognitive decline and dementia incidents in late life. Her work has employed advanced neuroimaging techniques to investigate associations between a range of modifiable, systemic health factors such as cerebrovascular disease, cardiorespiratory fitness and systemic insulin resistance and brain structure function in aging. Her current research focuses on broadening this approach to also consider socioeconomic determinants of dementia risk and cognitive trajectories in late life. Dr. Williams, thank you for being on the podcast.

Dr. Victoria Williams: It is my pleasure.

Chin: Full disclosure for our listeners, I work very closely with Dr. Williams in our memory clinic and I'm excited to have her on as she has frequently talked about this particular topic and done a wonderful job of educating our trainees that come through the memory clinic. So with that I'm going to go ahead and call you Tori going forward, if that's alright with you?

Williams: That is preferred. Thank you.

Chin: And I want to ask a basic question that I think is really important. What is cognition exactly?

Williams: That is a great question. Cognition is actually a term that refers to all of the conscious and unconscious mental processes that are involved in thinking, perceiving and reasoning. Cognition can be broken down into several different domains of cognitive functioning and these domains are organized in a hierarchical fashion. These domains include things like our ability to perceive sensory and tactile information, perceptual abilities, attention, language, memory and executive functioning. Bottom-level cognitive processes include basic sensory and perceptual abilities, so these are things like auditory, tactile and visual processing. These provide the brain with information about the external environment, as well as attention, which is a person's ability to appropriately select which relevant stimuli in the environment that they should be attending to. These more basic cognitive abilities really form the building blocks for the brain to carry out more higher-level cognitive abilities using this information, such as the ability to learn and remember new things, to utilize language and to accomplish things like higher-level reasoning and problem solving, which in our field we call executive functioning. This hierarchical structure means that cognitive domains are not independent of one another but instead they work together to accomplish cognition, with executive functioning representing the highest level of thinking ability, which is to exert control over the utilization of these more basic cognitive processes.

Chin: You mentioned the different cognitive domains. Are you able to geographically localize those domains on the actual brain itself?

Williams: So neuropsychology, which is the area that I trained in, is a field of study that really aims to link these observable cognitive processes to the underlying structure of the brain itself. The idea here is that different cognitive functions can be localized or are subserved by distinct regions or areas of the brain. For example, memory and language are highly dependent on the temporal lobe. Visual spatial abilities can be localized more to the occipital and parietal lobes of the brain, whereas executive functioning really largely relies on the frontal lobes. So neuropsychologists have developed these varieties of pencil-and-paper type of tests that are designed to specifically assess each of these cognitive domains. During a neuropsych evaluation, a patient is given a wide battery of these tests in order to assess their abilities in each of these areas. If an individual is consistently scoring low on tests within a single domain, it can provide the neuropsychologist with evidence or clues as to which part of the brain may not be functioning well.

Chin: Given the different domains that you’ve talked about, are there additional domains that you just don't test for or do you actually have paper-pencil tests for all the things you just mentioned?

Williams: Those are the core cognitive domains. As I mentioned before, we have attention, motor, sensory, language, visual, spatial, memory and executive functioning. I think those can cover all of the different cognitive processes. You know, some processes can span multiple domains, so for example something that requires working memory, it requires kind of both attention as well as executive functioning. The domains themselves are not quite as clear-cut as you would think, but in general the field has established those as the primary cognitive domains and then the tests are developed to look at different processes or different things that are within each domain.

Chin: Well you mentioned attention as a basic, or lower on the hierarchy, which I think is kind of funny because I think attention is so critical to all the things that we do. If you don't have focus, how can you do any of the other parts of the brain? So I guess that's probably why it's at the base.

Williams: Yeah.

Chin: And then you mentioned executive function, which I think is a really hard concept for people. Can you explain it perhaps in a different way that our listeners could understand, what exactly goes into executive function? How would someone know that that part of the brain may not be working as well?

Williams: Yeah that's a really great question. I would say the most general way to describe executive functioning is the ability of the brain to kind of manipulate information and integrate things and to exert control. For example, executive functioning can include things like being able to shift sets. So you have different rules that you're trying to go between. It's the control of the brain to be able to go to one rule and then to know that you need to switch back to another rule. Executive functioning also covers functions like complicated reasoning, judgment, problem solving, and things that require a lot of reasoning and higher level kind of integration of material to be able to arrive at an answer to solve a problem.

Chin: And executive function is usually found in the front of the brain, is that right?

Williams: Yes, exactly. It's kind of interesting. You know, one of the things that are quite unique to humans is our ability to use tools and to solve problems and to have this higher level cognition. The frontal lobes, evolutionarily, are the last things to develop but also what tend to take up the greatest part of the brain in humans. So the frontal lobes are very evolutionarily adept at carrying out these higher level cognitive abilities.

Chin: So it seems to me executive function really is quite critical in the whole thinking ability process and it is relatively a recent addition to the brain's ability. In a lot of ways, it kind of makes humans human. We're able to manipulate things the way other ancestors and animals cannot. I just want to make that clear that I have a good understanding of that.

Williams: Yeah, that's absolutely correct. The frontal lobes are highly developed in humans and really have kind of led the way to all these technological advances that we enjoy on a day-to-day basis.

Chin: I'm wondering in your assessment as a neuropsychologist, how do you incorporate intelligence, a person's background, their education level or their career path. Is that a factor in this analysis and assessment of people?

Williams: Yeah, so intelligence is a unique concept from cognition. Intelligence is basically a person's overall capacity for learning. The cognitive domains are more measurable and contribute to intelligence but, at the same time, intelligence is something that often develops early on in life and maintains relatively stable across the life course, even in the face of a degenerative condition or disease. So if you think about intelligence, it's kind of how much of a bucket do you have to fill up whereas cognitive processes are what allow us to do our day-to-day sort of thinking and reasoning.

Chin: And so knowing that, can one test, one paper-pencil test that you do, can it actually measure just one domain?

Williams: That's a great question. So as I mentioned earlier, all of these domains are very interrelated and hierarchical and dependent on one another. For example, something that really seems simple, if you want to look at somebody's language ability and to see how well they can come up with the name of an object. If you show them a picture of that object it seems pretty straightforward. Say you show them a picture of a pencil. They can either say it's either a pencil or it's not a pencil but really there's a lot of things that have to happen in the brain prior to that person being able to actually express that they're looking at a picture of a pencil. This is a really good example of that hierarchical structure where the first thing is you have to have intact perceptual abilities. You have to be able to look at a drawing and be able to process that image and basically get the information that you're looking at a picture of a pencil. You have to have the attention to be able to attend to that drawing to even, you know, look at it in the first place. And then from there, you have to kind of – then you have the language component, which is really what you're trying to get after with the task. You're trying to link an image or a representation of an object with its meaning and with its word so you would then really rely more on your temporal lobe at that point to link the image of a pencil with the name pencil. Then finally you have to have your expressive language ability also to be intact, which is being able to – once you come up with the word pencil being able to use your motor skills, you know, with your mouth in order to actually say the word pencil. The one thing we're trying to get at with that test is really the link between the picture and the meaning, but as you can see there's a lot of other cognitive processes that must be intact in order to get a correct answer on that one test.

Chin: That it's such a perfect example for our listeners. A pencil is not just a pencil. It clearly represents a lot more to the brain.

Williams: (laughs) Yes.

Chin: And this allows me then to have you explain, because I think this is such an important concept for people who will frequently come into our clinic and say I'm having a memory problem, having memory loss. We end up finding it's actually something else in the whole process of thinking. Can you tell us what is memory, and how does it actually work?

Williams: Yes, so memory is a highly complex cognitive ability. You know, the theme so far is that it really does rely on this range of other lower, as well as higher, level cognitive processes. If we first consider the lower-level cognitive functions, the basic, you have to have your basic sensory abilities intact to fully process what should be learned and remembered. For example, somebody with poor hearing, that may limit their ability to process the auditory information for which they're going to be asked to remember later, such as a story that they were told or a recent conversation. Having a hearing deficit can certainly impact your ability to remember information because you're not getting it in to begin with. As I mentioned before, you also have the attention component where the ability of the brain to focus on and select relevant information to be learned can differ whether you're in a quiet and distraction-free environment versus a really noisy shopping mall where you're trying to hear your friend talking and remember what they're saying. It takes a lot of effort to kind of focus on specifically what you want to remember. Having that intact sensory and attention ability is just a fundamental prerequisite for memory. As to the memory process itself, it can be broken down into three main stages. The first is encoding, and this is the brain's ability to actually form a new memory. We know that the hippocampus plays a really key role in this initial learning stage by transforming and linking these internal thoughts and external events into a form that can be stored into the brain later. The second stage, which I just alluded to, is storage. This is the brain's ability to actually maintain this memory over time. Finally, the third stage of memory is retrieval, which is the brain's ability to recall this information that was previously or initially learned. It's important to know that retrieval can be broken down further into two types, so you have free and cued recall. Free recall is your ability to spontaneously recall this information, which actually relies quite a bit on the frontal lobes to effectively find this intended memory to recall whereas cued recall is where you provide somebody with a hint to help locate that memory. On our testing, we might have a recognition task where you would ask them was this word on a list or was this word on a list and they would tell you yes or no. So you're giving them that hint or that structure. This really does reduce demands on the frontal lobe in the memory retrieval process. Those are the main stages of memory. I kind of have a good way to remember this, which is by comparing it almost to kind of a library system. In this analogy, initial encoding would represent the process of integrating information in order to write a book. So you're writing the book and in the writing process you're integrating all this information to create this book. Then storage is the process of placing that book on the shelf in the library in a way that you can easily find it later. And then retrieval would be the process of walking into the library again days later and being able to locate that exact book on the specific shelf where it was stored. However, you know, as you would know walking into a library with thousands of books, sometimes it can be difficult to know exactly where to look for that book. That's where the card catalog system comes in, which in this analogy would represent the frontal lobe. Memory retrieval is also reliant on this kind of cognitive control and executive functioning component to sort of guide the retrieval process, and so the frontal lobe would be the card catalog that would give you that hint or clue of where you would have to go in the library to find that book.

Chin: That is a wonderful analogy. Thank you for explaining that because the first part of your answer was a bit complicated. You know, a question that comes up a lot in clinic is, well where are memories actually stored? Is it all in the hippocampus, the “memory center” of the brain? Or why is it some memories more easily recalled than others? Can you speak to that?

Williams: That's a really hard question, but yes I do have some insight into that. The formation of a memory, it's not as a single cell or a single place in the brain where there's one specific memory, but it's really the pattern of activation of several different areas of the brain that then gets encoded and amplified. So the process of memory is a really complicated process but it involves synaptic plasticity. When you learn and remember new information, your brain is actually wiring new connections. Recalling that is re-experiencing that initial connectivity that you had for the initial memory in a way. You know, the hippocampus plays a really key role in being able to do that function. What's really unique about the hippocampus – so you asked about why are some memories easier to recall than others – that's because a hippocampus not only integrates the kind of facts of a memory, so where you were, what it was like, but it also integrates all different kind of experiential factors, so what did it smell like, what did it feel like, what was your emotional reaction when you were in that place at that time. It has really strong connections to our limbic system like our amygdala that generate emotional reactions. That's why sometimes even just an emotional response can generate memories because it's a strong linkage between an actual event and the way you felt during that event as well.

Chin: You know, I've actually heard in books that a memory trick is if you can try to tap into your other senses while you're trying to remember something, such as smell, sight, feeling, and you're just sort of explaining that right now. For our listeners, you did use the expression synaptic plasticity so I just wanted to explain for them. A synapse is the connection among brain cells because brain cells can communicate, so it's a place in space. They're not actually touching, but it's a place where all of those chemical signals like dopamine and serotonin can actually interact and be passed on. Plasticity meaning the ability to be modified or improved upon or worsened, I guess, but it's not fixed. That's actually something that can be changed. I just wanted to give that clarification but it also makes me think then, this is a really complex process. You just explained memory and took minutes to get through it. So how is it that cognitive testing can really get down to what is abnormal or normal? I mean, do you think cognitive testing is a perfect science or do you feel like there are areas that are certainly being worked on?

Williams: Yeah, so that's one of the things I sense in clinic all the time. These tests are pencil and paper activities and they're really designed to kind of get at these very core constructs of cognition, so very specific things like naming or generative, you know, very, very specific subcomponents of cognition. Oftentimes I have a patient in front of me and they're like, well what is this all for. You know, these seem silly. Why am I being asked to kind of come up with all  these words that you know within a category or remember this silly list of words. It's not necessarily the content that we're looking at but it's the process and the efficiency that their brain is engaging in that process. That's what we're really trying to measure but there is a gap. You know, there's an idea, a construct of ecological validity, which basically means how well does a test actually correspond to the construct we're trying to actually measure. That's always tough because we can't get into somebody's brain and take a ruler out and actually measure you know these certain kinds of thinking skills, and so this is really kind of the closest that we've gotten to this. As I mentioned before, it's not necessarily the content of the test itself in most cases but it's just how well the person can engage their brain in the process of doing that activity or that cognitive task.

Chin: You know, a question that comes up to me, as the physician who goes in after you do the testing, is how do you determine normal from abnormal? I'm my own person. I have my own life experiences. How do you determine these thresholds or how did the person who created the test actually determine what is not normal aging from what is normal aging?

Williams: Yeah, and that really forms one of the the basic principles of neuropsychology. All of the tests that we've developed in our field are what we call ‘normed.’ What that means is that these specific tests are given to a large number of people out in the general community and they're all asked to perform the test. Then their scores are combined and typically, if you're doing kind of a random selection, scores will fall into a nice bell curve or a normal distribution where most people are going to score in the average range right in the middle, but then you have your two tails so you have people that normally would score really high and normally score on the lower end of things. What you can do then is, we know that there's certain things that impact cognition that aren't related to disease processes. For example, as people grow older or age, we know that processing speed slows down a little bit. Memory can also decline a little bit with normal aging as well. So we want to make sure that we're comparing a person's score with what we would consider to be their peers. It wouldn't be fair to look at a ninety year old's memory performance and compare it to somebody who is twenty-five. What we do is we kind of take that normal distribution and break it down by certain bins. You know, we would look at a similar age range, a similar education level, a similar – sometimes even there's sex or gender differences in the way people perform cognitively. We try to as closely match that individual to their peer group or a comparison group and then we'll take their score and we'll place it on that distribution that's now been narrowed down to be considered their peers and see if they're performing below what we would expect, given all these other factors that are present.

Chin: And do you ever have to put in extra considerations, like anxiety during the test or the fact that it was a quiet room versus being at a loud grocery store or that they didn't sleep well the night before? These are things that I hear a lot and I'm just wondering, how do you account for that during your evaluation?

Williams: Yeah, and that's important. Interpreting test scores really does involve kind of a holistic approach. You know, factors that could impact test performance are always going to be present and they should be considered. Before I start my testing, I have a very thorough clinical interview where I'll ask a lot of questions about their mood, about their sleep. During testing, I can kind of sense whether somebody's feeling really anxious and so I may kind of take that performance with a grain of salt or consider that in my workup. Although these tests really do a fairly good job of localizing different cognitive functions to the brain, they can be often noisy. There are a lot of things that contribute to variations in scores that aren't necessarily reflective of their true cognitive ability. That's kind of the art of neuropsychology is being able to identify that and tease out all the factors to make sure that we're doing our best to really look at how that person is performing within a cognitive domain.

Chin: Then one other question about limitations – when you talk about the data being normed, meaning this is what we anticipate for a person of this age, I think some of the things that have come up more recently in the field, that that data, that baseline data, that the testing wasn't done in as many communities of color or based on geographic location or just life experiences, right. So if that's the data that's being used to be considered the baseline, are there newer studies that are trying to incorporate more representation and diversity in putting that normative data together?

Williams: Yes, yes, that is a good question and a great point. There is certainly a big push in my field to revise a lot of norms to be more culturally sensitive, to account for any racial or ethnicity differences in kind of the normal distribution of scores. Although the tests themselves have remained fairly stable, I would say, as far as the core kind of neuropsychological test battery, the norms are constantly being updated and revised and hoping to be as inclusive as possible. One of the great things is the whole Big Data push, so sharing data and collecting data from a wide range of people. Oftentimes those can inform our normative data as well. We're making progress in that area and it is an area that does need attention.

Chin: Well Tori, as you know, on this podcast we talk a lot about the exciting evolution in advancements in biomarkers, blood tests, PET imaging, spinal fluid, but as a clinician, of course, I always come back to the value and importance of neuropsychology and in thorough cognitive testing. So can you share with our listeners, if cognitive testing – and not brief ones but the kind that you do where it's 45 minutes to four hours – can you find patterns in those changes or impairments in those domains that may help you think of what the possible cause would be?

Williams: Yeah, absolutely. That also is kind of one of the fundamental principles of neuropsychology. As I alluded to earlier, there's this idea that cognitive functioning can be localized to different areas of the brain. That's kind of a blanket statement because there are some processes that are more distributed certainly, but we know from patients who've had strokes that affect a very specific region of the brain that they can lose a very specific cognitive ability yet all the others remain quite intact. That's evidence that there is a localization of function between cognition and the brain region that kind of supports it. Doing a thorough neuropsychological evaluation is really assessing every single cognitive domain and looking at the overall pattern or profile of performances. Generally, you would expect an individual to perform kind of similarly as far as their level. You know, average, low average, high average, across the different cognitive domains. That's kind of a reflection of their general Premorbid ability. What we're looking for, especially like in a dementia clinic for example, would be areas or domains in testing that are consistently lower than expected given how they're doing in all the other areas. What that would indicate to us is that that part of the brain may be not performing as well or not functioning as well, or there may be some type of pathology present that causes that lower score in that area. How that's useful is that it helps us determine the etiology, or what's causing the dementia. I'm sure your listeners may be aware that there's various types of dementia. Each type has a different mechanism on how it first exerts influence on the brain or what parts of the brain are first impacted in that disease process. For example, we know with Alzheimer's disease, the temporal lobes are the initially impacted brain region, the temporal lobes and Alzheimer's. We know that the temporal lobe is really important for memory and language abilities. Somebody who presents with early language and memory problems on neuropsychological testing would lead the clinician to think, well maybe there's pathology that's accumulating in that area of the brain. Because that's where Alzheimer's generally first starts to accumulate – Alzheimer's pathology starts to accumulate early on – it gives a clue as to, you know, this likely looks like a case of Alzheimer's disease.

Chin: What about Lewy body disease and typical vascular disease? If there's such a thing, what kind of patterns do you look for if you're suspecting that?

Williams: Yeah. Lewy body disease, we know that that pathology starts to first impact the parietal lobes. The parietal lobes are really important for visual-spatial ability and also for attention, so especially spatial attention in visual-spatial functioning. Oftentimes with Lewy body, we'll see early deficits on tasks that are designed to look at the ability for somebody to copy kind of a complex figure so you'll see some disorganization and some difficulty with the visual-spatial aspects of that task. For vascular dementia, for example – so vascular dementia is kind of an interesting story. Historically, vascular dementia was really defined by this acute or localized stroke that impacts this specific region of the brain and it causes an abrupt decline in that area, but over the years research has really supported this idea that there's also additional ways that vascular disease can impact the brain through more kind of subtle accumulation of these more small vessel sorts of infarcts. They call this microvascular ischemic changes, where the vessels become stiff, the little tiny capillaries in the brain and then that can cause leakage or can cause tiny little deprivations of oxygen in that area. It basically causes more minute and tiny little lesions but those accumulate over time. Once it reaches a threshold, you'll start to see changes due to those kind of more subtle vascular phenomenon. Interestingly with vascular changes, it really does tend to impact the white matter of the brain, which is really – a good example would be it’s the highway system of the brain. It's how the different areas of different lobes connect and talk to one another. When you have this accumulation of damage to this highway structure, the brain is not as effective at processing information so you see early problems with processing speed, attention and a lot of difficulty, also, with kind of executive, higher-level functioning because the frontal lobes aren't as well connected to all the different other regions they're trying to kind of integrate with.

Chin: This is so helpful. I hope for our listeners they can see the value of this more thorough testing. Two conditions come to mind that I know people look for in a clinic, but also when you're doing testing: sleep apnea and depression. Are there typical patterns or patterns you see more often in individuals who do not have Alzheimer's or vascular disease or Lewy body disease, but in fact, they have sleep apnea or depression that's causing their symptoms?

Williams: Absolutely yeah. Those are important conditions to look for because there's some of the few reversible causes of cognitive and memory loss. If we can identify those early on, one, it could rule out the diagnosis of dementia, but also it's a chance for us to intervene and to actually improve somebody's ability to think. We'll just start with sleep apnea. As we know, that's a common medical disorder. It's characterized by repetitive pauses in breathing during sleep. These breathing pauses can prevent your body from supplying enough oxygen to the brain and it also causes frequent arousals and that prevents you from achieving restorative sleep. Fragmented sleep, which is very common in sleep apnea, does impact the optimal functioning of your prefrontal cortex. This is an area, as we've discussed previously, that's really important for cognitive control and attention. Individuals with sleep apnea often present complaining of trouble – I can't pay attention, I can't focus. I'm having trouble with my memory. However, the way in which memory breaks down in sleep apnea is quite different from Alzheimer's disease. If we go back to those stages of memory we discussed earlier, Alzheimer's disease is best characterized by this trouble or difficulty with encoding, or the initial formation of a new memory, and as we talked about earlier this is due to damage from the hippocampus, so the ability to form that new memory. In sleep apnea, though, memory changes can be linked more to frontal lobe dysfunction, which leads to kind of inefficient learning and retrieval strategies. A patient with sleep apnea may have more difficulty employing an effective learning strategy, but what they do learn they generally encode it well and they can remember it well, especially if you give them a clue or a cue at the end. So yeah sleep apnea certainly can impact thinking, but the core memory encoding usually is intact. On the other hand, things like mood disorders, they impact how the brain works through an entirely different mechanism. Like we mentioned, depression is actually one of the few reversible causes of memory and thinking changes. As your mood improves, we would expect to see a corresponding improvement in cognition as well. This is why assessing for mood disorders is really a critical component of the dementia workup. Depression tends to cause slowed processing speed, difficulty with attention and concentration, as well as changes in your higher-level thinking such as learning memory and executive functioning as well. These cognitive changes, they can be due to a variety of factors but research has shown that depression is linked to an imbalance of neurotransmitters, as well as atypical patterns of connectivity between brain regions. Both of these stand to impact how information is processed in the brain. Slowed processing speed and executive dysfunction really can contribute to less efficient learning and retrieval as well. Similar to patients with sleep apnea, encoding is usually remains intact so the information they do learn they generally can remember later on.

Chin: And I've heard you say in clinic, too, that in someone with depression as the cause of the symptoms, usually across all of those domains that you're testing that are usually lower scores or globally depressed scores. Is that something that you do see frequently in clinic?

Williams: Yes, yeah. That can be due to a variety of factors as well. Certainly the slowed processing speed and the kind of direct impact of depression on the brain is a factor, but also patients with depression tend to be really apathetic and lack motivation. Sometimes it's even hard for them to feel motivated enough to perform at their optimum across domains as well. But again, if you think about the key cognitive domains that are impacted in depression, so attention, processing speed, those are some of those lower-level, foundational cognitive abilities that really limit how well those higher cognitive abilities will be able to perform as well.

Chin: We know, Tori, in the field there's more and more push to have better access, which is important, but also simpler ways to come to a diagnosis. I know that, you among other neuropsychologists that I'm friends with and work with, there's a pushback that we really can't diagnose people with a cognitive screener. For our listeners a cognitive screener is a Mini Mental State Exam (MMSE) or the MoCA, the Montreal Cognitive Assessment. These are good screeners and have a purpose, but I'm hoping to hear from you – and this is going to be your own personal opinion, I know this doesn't represent you, the whole field or certainly our institution – but why is it that we can't diagnose people with these tests and, if we can't, then what is their purpose?

Williams: Yeah, so that's a really great question. I think that there's a couple things to keep in mind here about the limitations for these cognitive screeners as diagnostic tools. The first is that they were never developed to be that. All of these tests were really determined to be, like you said, a screening measure to find people who may be at risk for dementia or cognitive impairment. These tests are not very sensitive, especially at the earlier stages of dementia or even mild cognitive impairment, so they do a really poor job actually of identifying people with mild cognitive impairment from people with normal cognition. There's several reasons why the tests are not quite as sensitive as we would like. The first would be that it's a measure of global cognition, so it basically takes one or two items from each different cognitive domain and it generates a total score. It basically takes our building blocks of cognition and collapses them into one lump sum. I feel like we've talked about throughout the podcast, that different medical conditions, different dementia etiologies, can cause differential impacts on the cognitive domains, so they're not all going to present equally. Diagnostically, it's not that useful at determining the etiology or what is actually causing the cognitive impairment. The other thing is  a lot of these were really developed in the area of memory and Alzheimer's disease, and so they really are heavily weighted – so out of all the total points, like the number of points dedicated to things like memory and orientation are a lot higher. There's only, I think, one visual-spatial item on the MoCA. And so, you know, say somebody has Lewy body and they have primary visual-spatial impairments, they could still score well within the normal range on one of these cognitive screening measures and it would completely miss the fact that they have dementia. It's just not capturing that domain well. I would say the other main limitation of these screening measures is that they rely on a cutoff score. I talked earlier about how, in neuropsychology, we have these really well-developed normative samples, so we can control for a person's education level, their age, their sex or gender, and even their race and ethnicity at times. The reason why we do that is because we know that all of these factors can impact how well a person does on a test. Well, the cognitive screening measures just have a cutoff score so there's no adjustment really for some of these well-known factors and that leads to both under- and over-identification of dementia. For example, somebody who is very highly educated and started at a really high level of cognitive ability, they probably have a lot of cognitive reserve, so an ability to compensate for some early changes in their cognition. So they may still score well within the normal range on the MMSC, yet if you were to give them a more detailed and comprehensive neuropsychological test you'd be able to see that there are actually deficits. On the flip side of that, somebody with really low education level maybe scored below the cutoff, yet that's just kind of their baseline and there's no dementia present.

Chin: Of course, something that we see a lot in the memory clinic is someone who comes in with a low cognitive screening test but it was done at an inopportune time or the person administering the test may not have been fully trained to do it or the person taking the test just wasn't prepared. Then they go through the thorough testing with you and they actually have intact cognition. There's just some caveats, I think, that people should be aware of as they are considering having a test and certainly what the test result means. It leads me to my final question, Tori, which is, we're in a time of incredible advancements in technology and artificial intelligence and digital tools and ipads and phones or tablets and phones. What do you think the future is for cognitive testing? You know, what are the newer tests going to be five years from now or ten years from now?

Williams: Yeah, and that's a great question. The field is certainly evolving. As you mentioned, digital testing is starting to become a lot more prominent in neuropsychology. There are some really distinct benefits to digital assessment. Part of that is really being able to capture more sensitive measures of cognition. A lot of things done digitally on an iPad can really easily capture things like reaction time or make actual quantifiable measurements for things that we can't do with our pencil and paper tasks. For example, there's a digital version of the clock draw test where it doesn't just give you a score on how well you draw the clock but it can actually capture the hesitancy of how long it takes you to do each part of the clock. Digital testing does offer a lot of areas of growth for the field. On the flip side, however, I will say just as a clinician and being able to sit with a patient face-to-face, you really do get kind of a sense of how that person's doing by interacting with them. I don't feel like digital testing could fully replace an in-person neuropsychological evaluation but it certainly could be incorporated and add on to what we already have in the field.

Chin: And with that I'd really like to thank you, Dr. Tori Williams, for being on dimension matters and helping explain cognition, memory, the strengths and some of the limitations of testing, and then, of course, the future of testing. I certainly hope you are never replaced by technology and I don't anticipate that, but I am excited about what the future of cognitive testing looks like and certainly memory care. Thank you for being on and sharing your knowledge.

Williams: Nate, it was such a pleasure. I really appreciated the opportunity to connect with your listeners and thanks for having me on.

Prerecorded Dr. Nathaniel Chin: As a reminder, continuing education credit is available for this episode through the Interprofessional Continuing Education Partnership at University of Wisconsin–Madison. To claim credit, you can text this code: BUSFOV at this number 608-260-7097. Again the number is 608-260-7097 and text this code: BUSFOV. Your feedback is important to us. To complete an evaluation form for this episode, see the show notes.

Outro: Thank you for listening to Dementia Matters. Follow us on Apple Podcasts, Spotify, Google Podcasts, or wherever you listen or tell your smart speaker to play the Dementia Matters podcast. Please rate us on your favorite podcast app -- it helps other people find our show and lets us know how we are doing. If you enjoy our show and want to support our work, consider making a gift to the Dementia Matters fund through the UW Initiative to End Alzheimer’s. All donations go towards outreach and production. Donate at the link in the description. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center at the University of Wisconsin–Madison. It receives funding from private, university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's Disease Centers. This episode of Dementia Matters was produced by Amy Lambright Murphy and Caoilfhinn Rauwerdink and edited by Alexia Spevacek. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. To learn more about the Wisconsin Alzheimer's Disease Research Center and Dementia Matters, check out our website at adrc.wisc.edu, and follow us on Facebook and Twitter. If you have any questions or comments, email us at dementiamatters@medicine.wisc.edu. Thanks for listening.