Thank you very much for coming. The title of our symposium is It All in My Head, Subjective Cognitive Impairment in Neuropsychiatry. I'd like to thank the program committee of the APA for allowing us to give this symposium. And I would also like to thank my co-presenters, Dr. David Friedman and Adriano Molica. They're both PGY-4 residents in the training program at the University of Toronto, both in the clinician scientist stream. David is training with Dr. Anthony Feinstein, who I earlier did a neuropsychiatry fellowship with, and Adriano with Dr. Matthew Burke. My name is Omar Ghaffar. I am a humble clinical psychiatrist. I work in CL psychiatry in a post-acute care setting, so in a 500-bed rehabilitation hospital. I also see a variety of neuropsychiatric patients, that is psychiatric care of neurological patients, individuals with acquired brain injuries, neurodegenerative disorders, and functional disorders. None of us have anything to disclose. David and Adriano are residents, so they have no money. More importantly, no financial relationships. I just stepped out for a breath of air while we were waiting and kind of got lost in this maze of a building here, and briefly panned It turns out that minor cognitive lapses, memory slips, word-finding difficulties, things of that nature are quite common in the general population. So this is an example of a survey trying to assess the number of people who are experiencing cognitive lapses in the general population. This is a survey trying to establish a quote-unquote base rate of cognitive symptoms in young, healthy controls. So these are people who are dwelling in the community. And you can see that the symptoms run the gamut from forgetting telephone numbers or telephone conversations. I'm sure everyone is struggling with PINs and keeping track of various bank accounts. I have an entirely separate job managing these for my parents. Forgetting why they came into a room, forgetting what we had for breakfast, or where we parked the car. Some of these are in the order of one third of normal, healthy 30-year-olds. I think one of the questions that we want to explore a little bit today is, given this, what is it that leads some people such distress and impairment around some of these issues and leads them to come to clinical attention? Is it that their deficits are more severe? Is it that they're more pervasive? Is it that they had an injury before and they're worried about the implications of that? So these are some of the things that hopefully we can broach a little bit today. So to that end, our learning objectives are to describe subjective cognitive impairment in SCI and its relationship to objective cognition, to analyze the potential contributors to SCI in a patient with MS, and to develop an appropriate management plan, to characterize SCI in a patient with mild traumatic brain injury and develop an approach to management, and then finally to explore the concept of functional cognitive disorder as a transdiagnostic lens or a sort of heuristic for understanding subjective cognitive impairment. So what is subjective cognitive impairment? Louisa is a 34-year-old woman presenting with two years of worsening forgetfulness and associated anxiety. Her past history includes major depressive disorder treated with sertraline, quetiapine, and CBT and two previous concussions. You complete your comprehensive assessment, and at the end, you ask, do you have any questions? And Louisa replies, so, is it all in my head? So we'll come back to Louisa. What is subjective cognitive impairment? So there are a range of descriptors that we can find both in the literature and in the popular media. Neuroesthenia, brain fog. There was a recent Reddit analysis of brain fog in a paper in the JNNP really describing a range of experiences from forgetfulness to cognitive fatigue to what sound like dissociative experiences. Chemo brain in individuals who've had chemotherapy, cognitive slowing, fuzziness, et cetera. The list goes on. Mild cognitive impairment is a really important construct, I think, when we're thinking about subjective cognitive complaints. And finally, functional cognitive disorder, which you may have heard of. I'm just curious, has anyone heard of it? So a few people, so it will be interesting to talk about it together. Stewart defines subjective cognitive impairment as the occurrence of a person reporting or admitting to cognitive function that they feel is impaired. Question, does this pertain only to memory or other cognitive domains as well? I will answer, other cognitive domains. And we'll speak more about this as we get into the talk. Does it require the absence of objectively measured cognitive impairment? Yes, but some people can have mild findings, things that are inconsistent and difficult to reconcile. You may see it on one test, but not on another test that's testing the same function. Should it be called subjective cognitive decline or complaint? Well, the words that we use are really important. These are different words. Decline implies a change over time, whereas complaint, regardless of how you may feel about describing what patients say is complaining, refers to, I think, more of a cross-sectional report. And how does subjective cognitive impairment differ for diverse neuropsychiatric conditions? Cognition can be defined as the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses. We can measure cognition, as you know, with screening tools, most commonly, at least in my hospital setting, the Montreal Cognitive Assessment, but there are others, the MINICOG, the MMSE, individual neuropsychological tests like the Boston Naming Test or the California Verbal Learning Test or others, and neuropsychological batteries, the RAO, brief repeatable neuropsychological battery is an example of one that's used often in MS, but there are many, often deployed in the context of detailed neuropsychological testing by a clinical neuropsychologist. So to try to get at some of these issues, we're going to talk about subjective cognitive impairment really across a spectrum of three big areas. First, multiple sclerosis, where there are demonstrable brain lesions, brain atrophy, traumatic brain injury, specifically mild traumatic brain injury, where the presence of lesions by conventional measures is usually, with some exceptions, absent in mild traumatic brain injury. And then finally, think about subjective cognitive impairment in the context of functional cognitive disorder. So without further ado, my colleague, Dr. Friedman. Thank you, Dr. Ghaffar. So I'm Dr. Friedman. I'm a fourth year psychiatry resident in the clinician scientist stream at University of Toronto, working with Dr. Anthony Feinstein with a particular research and clinical interest in multiple sclerosis psychiatry. And today, what I'm presenting on is subjective cognitive impairment in multiple sclerosis. So I like to always start with acknowledgments because I don't think it's an afterthought. I think really the work that I'm presenting today is a reflection of a tremendous amount of collaboration, learning, and mentorship from many individuals, including Dr. Feinstein, but also many other collaborators that we've worked together on research with. And so we'll start off with a fictional case grounded in some prior clinical experiences, but all fictional. So this is Kyle. He's a 42-year-old man with relapsing-remitting multiple sclerosis, financially supported by short-term disability coverage from work as a financial manager. He was referred by his neurologist for memory complaints and depression and anxiety. And Kyle, when you see him, reports, it's been a tough year emotionally. We just had our son Scott, and it's been difficult to look after him. I relapsed in August, and that created a whole host of issues. I often forget where I'm supposed to be doing with him and worry about tripping over objects while holding him. I'm exhausted all the time and can't follow conversations or multitask in meetings at work. I feel like I'm letting my wife and kids down. So although fictional, this does reflect the presentation of many of the individuals we see in a multiple sclerosis setting, where there's this confluence of multiple things, including cognitive concerns, mood, anxiety concerns, and also mobility and the other elements of physical disability that emerge in this context. So what is multiple sclerosis? Recognizing I'm at a psychiatry conference, MS is an immune-mediated neurological condition where myelin, the neuron cover, is damaged, resulting in various neuropsychiatric sequelae. And we know that in MS, there are a few different disease courses. So there's relapsing-remitting MS, where people have relapses and then the illness remits. There's secondary progressive MS, which often is a transition from relapsing-remitting, where the illness begins to take on a progressive course, even in the absence of relapses, although some can occur in the midst, often in the earlier stages. And there's primary progressive MS, which begins with this progressive, gradual accumulation of disability over time. And why am I talking about MS at the APA? What we know is that this is a condition characterized by an incredibly high burden of neuropsychiatric sequelae. 30% to 40% of people with MS have depression, 13% to 32% have anxiety disorders, and people with MS are at higher risk for bipolar disorder, OCD, suicidality, and many other psychiatric conditions. And these reflect more conservative estimates. There are some estimates that creep up to the span of 50% or 60%. And even from clinical experience, there are many patients in these clinics, in the multiple sclerosis clinics, that are struggling with psychiatric conditions as well. So what do we know about subjective cognitive impairment in MS? What we know is that it's present in 19% to 71% of people. This is a huge range, but I think reflects the early stages of evidence that we have on this topic. And there's similar levels of SCI intensity are present across disease duration. So we were able to find that whether it's in the first five years or whether it's at greater than 10 years following diagnosis, there's very similar levels of SCI intensity in this population. What we know about SCI is that it's also an independent predictor for worsening quality of life. It can lead to decreases in social satisfaction and participation in roles, relationships, and activities. And it also is a predictor independent of objective cognitive concerns or objective cognition of unemployment and reduced work hours. So it has a very meaningful impact on this population, often that are in their early years, between the ages of 20 to 40 or 50. And in its contribution to unemployment, that can have a major impact on the quality of life and their functioning and their role in society. So thinking about subjective and objective cognition in MS, we know that the prevalence of cognitive impairment in MS is in the range of 34% to 65%, with a higher prevalence in progressive forms of the illness. And we know that the most common deficits, which make sense in the context of effects on myelin, are common deficits in processing speed, memory, and executive function. Impairment, notably, is commonly missed using non-MS tailored instruments, like the MMSE or the MOCA, really highlighting the importance of using cognitive tests tailored for this population that can capture that aspect of processing speed. And we know that most studies that have looked at this topic support a weak association between subjective and objective cognitive dysfunction. And we don't know yet whether SCI can predict future objectively measured cognitive deficits. This discrepancy between subjective and objective cognitive dysfunction creates a real conundrum for a lot of clinicians. Objective cognition explains part of the story, but certainly not all of it. So looking into the literature on subjective cognitive impairment, we know that there's a number of factors that can contribute to someone's presentation in the context of multiple sclerosis. This includes predisposing factors, such as neuroticism, disease course, or sex. This includes neuropsychiatric symptoms that are incredibly common in this population, like fatigue, depression, or anxiety. Many of these patients have sleep disturbances and experience a tremendous degree of polypharmacy because of just the several different concerns they might have related to cognition, mood, bladder, spasticity, motor concerns. The drug list and the medication list can really increase quite quickly. They can experience objective cognitive impairment. There's thalamic demyelination and cortical connectivity changes that can contribute, and also gray matter atrophy. So we know that although this is predominantly thought of as a white matter illness, there is a tremendous amount of gray matter changes that are also occurring, and particularly in the thalamus that's been implicated, along with the hippocampus and the cortex. So in the context of this, what are the principles for managing SCI? And I'll highlight that this is really a tentative and preliminary sort of idea of principles that have emerged in the literature. Because like I was saying before, there really is not a lot of clear-cut evidence. It's still in its very early stages of research. But these are the principles that emerged in the literature of how do you manage SCI in this population. So the first principle is providing psychoeducation. What this involves is really validating their experience. People with MS are often struggling with distressing experiences, even right from the point of view of disease onset or diagnosis, where their concerns can be dismissed very early on. And so it's very important to incorporate a validating lens. There is evidence from Romero and colleagues that cannabis use can actually increase subjective cognitive impairment and have adverse effects. So we often recommend avoiding cannabis use. This is complicated in the MS population, as many individuals turn to cannabis as a way of also helping to address some of the spasticity. And so it is a balanced discussion. It's a risk-benefit discussion around positives and negatives, but something to consider. And finally, discussing cognitive coping strategies can be an essential element, either compensatory or other methods of coping with their cognitive concerns and maintaining their functioning. Next is measuring and assessing for objective cognitive impairment. Like I said, there is a weak association, but there is still an association. So it's important to take these concerns seriously, understand them, recognize the objective cognitive impairment concerns, while still considering all the other factors that could be contributing to subjective cognitive impairment. So to assess subjective cognitive impairment, you can consider the perceived deficits questionnaire, which is often used in this population. For cognitive screening, they often recommend the SDMT. It's a measure of processing speed. I always find it helps to have a picture. This is the test where there's a series of symbols in the top, and there's a series of numbers, or flip that. And you have to identify which number corresponds to which symbol, going from the top chart to the line. And then also, for further cognitive assessment, the most common validated neuropsychological battery is the minimal assessment of cognitive function and MS. But of course, this will rely on the resources at your particular setting. It's also important to address the underlying causes. So this includes things like treating depression, anxiety disorders, and fatigue, managing potential contributing conditions, as highlighted before, and reducing prescribing cascades. So I highlight this chart, which is from one of our recent papers looking at the neuropsychiatric status of patients with multiple sclerosis across disease duration intervals. And what you'll notice is that at longer intervals of disease duration, people with MS tend to accumulate a tremendous amount of polypharmacy. So by greater than 10 years, it is above 70, close to 80% of participants were receiving some form of psychotropic treatment. And many of them are receiving multiple forms. So they can accumulate antidepressants, stimulants, hypnotic or sedative medications, antipsychotic medications, mood stabilizer medications, and even pain modulating medications as well. In terms of thinking about psychotherapy or non-pharmacological options, the evidence is very weak. But I highlight that there is low quality evidence for CBT or supportive emotion-focused therapy for the treatment of depression in people with MS. Then that can improve subjective cognition. And there's some inconsistent evidence regarding neuropsychological rehabilitation. So still further research is needed. And no literature comparing these interventions. Now, in medication trials, this is where I think a lot of this has been evaluated as secondary measures in other clinical trials. This is very limited evidence. Subjective cognitive impairment was not the focus of these studies. But what it highlights is that in all of these studies, medications like memantine, denepazil, amphetamine medication, modafinil, and paroxetine had no significant benefit in these groups. So it does really highlight the importance of those elements of psychoeducation, the importance of those elements of addressing underlying causes and taking a holistic understanding of who you're addressing, and considering whether there's any psychotherapeutic options that could be beneficial. So coming back to the case. So this is really to give you a chance to think about many of the things we just brought up. When we think about Kyle, we can identify many different aspects that we talked about in MS that could be contributing to why he's experiencing subjective cognitive impairment, and that can inform how you might manage him, how you might address his concerns, and how you might ensure that it's a validating experience when this can be an incredibly distressing experience to feel as though your memory is failing you. So it brings to the conclusions. Subjective cognitive impairment is common and persistent in MS, and adversely impacts quality of life, community integration, and employment. This should broadly explore for potential contributors subjective cognitive impairment using your existing biopsychosocial frameworks. And this is really where psychiatrists can be at the front line, already using these frameworks to understand many of the other patients we see. And in the context of a limited evidence base, management of SCI may involve the following principles, which includes providing psychoeducation, measuring SCI, and assessing for objective cognitive impairment, addressing underlying causes, and considering psychotherapy or neuropsychological rehabilitation in that process. Thank you, everyone. And I invite my next speaker to come up. Hi, everyone. Thank you for being here. So I'm Adriano. I'm also a PGY-4 resident at Toronto with David. And so today, I'm going to be focusing on subjective cognitive impairment after a mild traumatic brain injury, as well as some of the other concerns that come up in the MTBI population. And I'm going to jump right into a case. This is Hannah. She's a 34-year-old health care worker. And she sustained a concussion after a bicycle accident about three months ago. At the time of injury, she had GCS-14. There was no loss of consciousness, though. A CT head that was done at the emergency department shortly after her injury was negative. And by this point in time, I mean her initial concussion symptoms have largely subsided, the dizziness, nausea, photophobia, phonophobia. But she is having these ongoing symptoms, headaches, insomnia, mood changes like irritability and anxiety, and as well as cognitive symptoms, which for her, she states is the most bothersome. Her family doctor from the time of injury and with her ongoing symptoms, and by the time before she's able to arrive in our clinic, her family doctor was able to arrange for an MRI, which was also negative for any changes. She's been off work for two months. And she tried to go back about a month ago, but just had real trouble with return to her duties. And you ask her to describe some of her cognitive symptoms, and she states the following. It's like I'm in a fog. I can't focus. I forget things I used to remember easily. My brain just shuts down on me. On your mental status, you noted her to be fairly tense and kind of anxious, which would be understandable given the concerns that she's bringing up. You're able to do a MOCA with her in the clinic, and she scores a 28 out of 30. She loses a point for delayed recall, which she's able to get with cueing, and misses a point on serial sevens. The only past medical history that I'll note is major depressive disorder that was treated with sertraline, but at this point, she's been in sustained remission for many years. She's not on any medications currently, no other past medical history. We'll come back to Hannah. But first, I'd like to just talk about what constitutes a mild traumatic brain injury. And this definition is evolving. Actually, just earlier this week, the American Congress of Rehabilitative Medicine just put out a new definition, so I would recommend looking at that. But the definition, the core of it hasn't changed all that much from 1993 when they put out the original definition. A closed head injury, largely with a normal imaging, that's the part that's changed, actually. So if there are abnormal findings on imaging, that can be included as a subset. There's no or brief loss of consciousness, and the alteration of consciousness, or if there's post-traumatic amnesia, it should resolve within 24 hours, and the GCS should be 13 and up. But even from this definition, you can see concussion and mild traumatic brain injury, which I'll use those terms interchangeably, they encompass a wide range of severity. And there's a lot of heterogeneity in this group, and that's sort of limited consistency in terms of diagnosis and some of the generalizability from this patient population as well. But it's an extremely common condition. Mild traumatic brain injury affects millions of people across the world, and traumatic brain injury does, and the vast majority are mild. And following a concussion, people can experience a wide range of symptoms that tend to kind of cluster in these three categories, particularly somatic symptoms like headaches, insomnia, fatigue, visual and vestibular symptoms, changes to mood, depression, anxiety. PTSD is also very highly comorbid, especially given the nature of the injury in some cases, and difficulties with certain cognitive domains. Now the vast majority of cognitive symptoms resolve in the first several weeks of following injury, but there is a subset of patients that can go on to experience persistent symptoms, which has been labeled as a post-concussive syndrome. It's thought to affect at least maybe 10% to 30%. Estimates vary, but the risk factors seem to be female, non-white ethnicity, poor pre-injury mental health, substance use disorder, if there's a history of chronic pain or history of somatization. And we don't have a clear biomarker in this patient population. What is it that differentiates the patients who recover after a mild traumatic brain injury versus those who go on to develop post-concussive syndrome? But it is thought to be that there is a disruption across several large-scale neural networks that regulate attention, emotion, sensory motor function, and cognitive control. And earlier this year, one potential biomarker could be this hyperconnectivity between the thalamus and areas of the cortex and other areas of the brain that's implicated. That might distinguish this group, and that's what's shown on the left here. So the areas in red represent hyperconnectivity in diffuse areas of the brain. That's one thing to note. And between those areas and the thalamus, a certain nuclei of the thalamus. And if those changes are present early on in following a concussion, that seems to be a biomarker potentially for patients who go on to develop post-concussive syndrome. Another important area to mention is the cingulum bundle. So it's a large white matter tract that seems to be commonly affected after a concussion. It's particularly vulnerable to injury. And areas where it's damaged, where it links up with the salience network and connects salience to the default mode network, which are some of these large-scale networks in the brain, seem to correlate with deficits in sustained attention. So in terms of assessing the cognitive symptoms in following concussion or following in terms of post-concussive syndrome, the main takeaway from this slide is going to be that there's a difference between the subjective cognitive symptoms that a patient reports and the objective tests that you would use to further explore those findings, those symptoms rather. On the subjective cognitive measures side, the Rivermead is probably the most commonly used. Very easy to administer. It's kind of like patients will rate the severity of their symptoms across a wide variety of categories on a scale of 0 to 4. Post-concussive symptom scale is very similar, and there's others listed at the bottom. And then this is certainly not an exhaustive list of the cognitive measures, the objective cognitive measures. These are just some of the ones that tend to pop up the most commonly in the literature. And there's a sport concussion assessment tool, the SCAT, which is kind of nice because it integrates both subjective and objective measures in the same tool. But what can we say about the cognitive impairment in post-concussive syndrome? This scoping review that came out in 2017 concluded, after reviewing 45 studies looking at this, that following a single concussion, approximately 50% are cognitively impaired on neuropsychological testing at one year. That's a pretty stark message. The only thing, though, is that it's not entirely accurate. So a group of expert neuropsychologists re-evaluated all 45 of the included studies with more tightly defined definitions and concluded that the impact of a single concussion on neuropsychological test performance becomes largely undetectable at the group level by three months post-injury in the vast majority of patients, and that a very small subset still have impairments at the 12-month mark. So it's a little bit more reassuring. But how does that translate? How do group-level changes translate to the individual person in front of us? So let's return back to Hannah. So looking at her MOCA, 28 out of 30 isn't too bad. Actually, it's a normative result. But perhaps for her, it does represent some kind of change from baseline. The MOCA maybe is not the best screening tool, actually, as well. It's great for if you're looking for dementia. But maybe for a high-functioning, healthy 34-year-old, maybe it's not the best to capture some of those changes. Let's say that she goes on to have neuropsychological testing. And let's even say that she performs one to two standard deviations below the expected mean in some areas, like verbal memory or processing speed. Would that fully explain the degree of reported cognitive symptoms and the functional change that she's experiencing? Some other important questions that might come up, would it mean that she's permanently cognitively impaired? Is this her new cognitive baseline? It's important to note that the changes in those cognitive domains also tend to overlap with depression, which is quite comorbid in this patient population. So what we'll need to ask is, what else could be contributing to the cognitive symptoms she's experiencing? And earlier in the STEM, there was mention of these ongoing symptoms, particularly headaches, insomnia, irritability, and anxiety. And that's really important. And across the literature, it's very consistently reported that the higher the affective and somatic symptom burden after concussion, the greater the correlation with subjective cognitive impairment and cognitive symptoms. Moreover, the association between objective test results and subjective symptoms reported by the patient is often reported as statistically significant, but with a weak correlation or negligible effect size. Another interesting point is that the improvement in cognitive symptoms, or subjective cognitive impairment, strongly correlates with improvement in emotional and somatic symptoms, not with improvement in objective cognitive test results. The presence of objective cognitive difficulties, if they're present after concussion, it actually more strongly correlates with the presence of current major depressive episode. There's also some other interesting psychological factors that might be at play that are influencing the patient's performance on tests. And so I highlight this study, which is pretty interesting, the influence of negative expectations. And what they did in this study is patients who had a remote history of head injury underwent neuropsychological testing. They were not experiencing cognitive symptoms at this time of assessment. But one of the groups, before their testing, their attention was brought to their history of head injury and how that might negatively impact their cognition. And what they found is that that group performed, even though the groups were the exact same, they performed significantly worse on neuropsychological testing. So it's important to keep in mind that the tests are measures of behavior and can be influenced by non-neurological factors. Another concept that's really interesting that's emerging in the literature is this idea of memory perfectionism that's been strongly associated with persistent memory complaints after concussion. And this has to do essentially with the intolerance of what is likely normative gaps in attention and memory that become a lot more noticeable following concussion. So to pull this all together just for right now, cognitive symptoms after concussion and in post-concussive syndrome are interwoven and difficult to disentangle in the polysymptomatic patient. Objective cognitive measures are, there might be findings, but they're often only weakly correlated with cognitive symptoms. And it's actually the affective and sleep and somatic symptoms that are more strongly associated with the cognitive complaints or concerns, rather, and better account for that discrepancy between objective test measures and the symptoms that a patient is reporting and so should be triaged in terms of management. So let's say that you share that with the patient and that there are these other factors that could be affecting their cognition, and they ask this question. So is it all in my head then? And I think this is an important question that gets at a few things. One I think is there's a subtext here, which is, are my concerns being dismissed? Are you just talking it up to anxiety? And it's also a symptom of a broader problem in medicine, which is that this is kind of tricky with non-specific symptoms. It's, we don't have a great way of validating those experiences, especially if the tests that we do are largely normative. But what it's also getting at is that, I mean, these symptoms are part and parcel of damage to the brain. Concussion impacts, as I said before, widespread neural networks that don't separate out into what's the psychiatric symptoms of the brain and what's the neurological symptoms of the brain after injury. It's all under the same roof. It shares the same house. And so there are important predisposing, precipitating, and perpetuating factors that will influence somebody's experience of the symptoms that they might be contending with. The other thing that's important to highlight is that, because there's likely in this case for subjective cognitive impairment after a concussion, if there are changes due to widespread neural network dysfunction, the brain is resilient and there's a potential for neuroplasticity. So these impairments aren't necessarily permanent. There's a lot of potential and opportunity for networks to change and for recovery to happen with the right kind of intervention and treatment. And I think it's important to validate but also highlight this hopeful and optimistic message, especially, as I said before, what we know about the detrimental effects of negative expectations on someone's cognition. I highlight this, which is sort of a non-pharmacological approach to management of mild traumatic brain injury that we published last year. And the idea here is really just to focus on the, after you do a comprehensive evaluation, the course, figure out what the core symptoms of post-concussive syndrome are and try to triage those. Mood changes, insomnia, post-traumatic headache. And while the mainstay of treatment is non-pharmacological, medications, there's some emerging literature, but there's also a paucity of literature. Methylphenidate, for example, there's promising results, but there's really only one double-blind placebo-controlled trial, and it's a small sample size, 32 patients. Amantadine, less promising. The only double-blind placebo-controlled trial that was done was negative. And acetylcysteine, there's some promising potential data coming out as well. And there's more mixed evidence for omega-3 and melatonin. So hard to know exactly where the medications stand, but that's sort of the available data for some select medications that you might come across. Cognitive rehabilitation. This is by no means an exhaustive list. There are many other cognitive rehab programs. I highlight COGSMART, though, which is a 12-week intervention that focuses on learning compensatory strategies for attention, memory, executive function that had significant improvements in post-concussive syndrome, or rather, sorry, in terms of post-concussive symptoms like cognition and perspective memory that translated to work attainment in a 12-month follow-up study in veterans. And it's freely available. So I've no relationship with this company, but just the idea that you can go to that website and download and attain a cognitive rehab strategy. Particularly if you are strapped for resources, that could be one potential resource. Other emerging programs are computer-based cognitive training, which is this is a paper that came out recently using tailored computer games for specific cognitive domains that increased in difficulty. And there's promising results from that as well. Improved cognitive function that was sustained at three-month follow-up. Another interesting emerging area is neuromodulation, transcranial magnetic stimulation, which there are promising pilot studies. I mean, they're small studies, but particularly for depression and for the management of headache and post-concussive syndrome, there are some early promising results. There's only one study that looked at TMS for cognition, but it was concurrent with depression as well. So it's hard to know what was really driving the effect there. But given that, I'll just go back to this. But given that, again, thinking about the network dysfunction in this patient population, there's good rationale to further explore a treatment that can directly potentially modulate some of that network dysfunction, particularly as we get a better understanding of more specific targeted areas. Another interesting area that's being explored are music-based interventions. So thinking outside the box a little bit, but music is a very enriching stimulus for the brain. There are many areas of the brain that can be simultaneously activated by engaging in music. And this study by Vick and colleagues used piano exercises with increasing difficulty in a post-concussive syndrome. And a post-concussive syndrome population that had gone through a lot of other rehab up until that point. And I think it was a small study. So I mean, I think there are seven patients. But in six of those seven patients, there were significant improvements on tests of verbal memory and a translation with functional improvement and return to work. So I think it's a promising intervention that was also correlated with a number of changes in neural networks that have been implicated in post-concussive syndrome. So this could be a potential emerging treatment that needs, I think, warrants more exploration and research. So just as a summary, the vast majority of cognitive symptoms following a concussion are likely to resolve in the weeks to months after the injury. However, persistent and distressing subjective cognitive impairment is common after a concussion and mostly involves these domains. And so it's important to validate that experience for patients. But the objective cognitive difficulties, if they are present, and the subjective cognitive symptoms that a patient is endorsing might be best explained by ongoing affective and somatic symptoms, which are very prevalent in this patient population and require targeted treatment. And just to say, neuropsychological testing does have an important role in this patient group, but the results should be interpreted in the context of its limitations and potentially contributing psychological factors. And then just that emerging treatment options still need to be explored, but some to consider are cognitive rehabilitation, neuromodulation, and music therapy. And here are my collaborators. And I'll turn it over to Dr. Ghaffar. Thank you. Thank you so much, Dr. Friedman and Dr. Mollica, for those scholarly reviews and for your contributions to this literature. I'll be speaking about functional cognitive disorder, which is a relatively new construct. Before doing that, I just want to kind of summarize my take-home points from what David and Adriano have told us. And I believe they have microphones, so feel free to heckle me if I say anything that is not consistent with what you presented or what you understand. But what I took away is that subjective cognitive impairment in MS and in mild TBI, that should read mild TBI, is generally poorly correlated with objective measures of cognition and with conventional measures of brain pathology, be that CT or conventional MRI. Subjective cognitive impairment in these populations may be more closely allied with premorbid personality, mood, anxiety, psychosocial stress, situational factors. Many of us see people after traumatic events, be they motor vehicle collisions or accidents or awful diagnoses or what have you. Somatic symptoms, so Adriano talked to us about a lot of distress occasionally or often being tied to things like headache and sleeplessness. Patient expectations for what their disease course is going to be can be potentially important correlates of subjective cognitive complaints. And then finally, MS and mild traumatic brain injury are both incredibly heterogeneous within them, even within a given disease course in MS and disease duration. There is tremendous difference between different individuals in terms of lesion load and distribution and measures of atrophy. Similarly, as Adriano pointed out, I think it's really important. Mild TBI or concussion refers to a hugely variable group. Someone who bumps their head and has no loss of consciousness, no post-traumatic amnesia is very different from someone who loses consciousness or has a period of post-traumatic amnesia for 25 minutes. They would both be categorized as mild, but these are different things. There is some literature actually suggesting the consequences of brain injury obviously are due to the kinds of brains that are injured, the mechanisms of injury, but maybe obviously other medical factors, but maybe also the kinds of necks in terms of the injury. So we did a workshop at the American Neuropsychiatric Association to remind us how to examine the neck. In any case, regardless, in both MS and mild TBI, subjective cognitive impairment can be a significant source of stress, distress, impairment, and poor quality of life, therefore potentially an important target for intervention. The treatments today in both cases are largely based on psychoeducation, supportive measures targeting comorbidities that may be contributing, so being thoughtful about making sure we're addressing mood, anxiety. I didn't put trauma or PTSD, but that's obviously included. Sleep, psychosocial issues, which are obviously very common, family conflicts, role changes, all of these sorts of things that can happen in the context of injuries can be quite helpful. And this is kind of our bread and butter. Most importantly, to me anyway, I think these interventions, or whatever we do, needs to be done in a validating and supportive environment with a really good therapeutic alliance. Adriano and David both mentioned some very tantalizing studies. And in the case of Adriano regarding neurologic music therapy, TMS, potentially there'll be good targets for pharmaceutical manipulation. But at this point, my perspective on this is that there's really no compelling, specific, well replicated kind of standard of care treatments, specifically for subjective cognitive impairment in MS or mild traumatic brain injury, aside from a careful, thoughtful assessment in targeting these comorbidities. Shifting into functional cognitive disorder, I'm going to start by reintroducing us to our friend Louisa. Louisa's fictional, but she's actually based on kind of a mix of patients I've seen. But I've tried to add a bit of detail around her case to try to bring it to life. I'm then going to propose, as many are doing and have done in the literature, that we think about potentially functional cognitive disorder as a subtype of functional neurological disorder. So I'll say a bit about functional neurological disorder and the history and development of that area, which has really been remarkable in the last 10 years, I think, for anyone who's working in medical psychiatry or neuropsychiatry. It's really a very different area than it was, let's see, 20 years ago when I presented my first fMRI paper on conversion disorder here at the APA. Things are very different now. We'll talk about some proposed pathophysiologic mechanisms very generally, and then some principles for treatment. And then reflect a little bit on what might we think about or expect in the future around this construct of functional cognitive disorder. So we met Luisa. She's got some cognitive complaints and some anxiety. There's a history of depression, treated with sertraline and CBT and two previous concussions. So you don't have to read this. I'll just say it. These are just details around her case. She was born in Mexico, no birth complications. She's the eldest of two, has a brother two years her junior. Her mother died in a single vehicle MVA when her mother was in her late 30s. Luisa was around six. But what we would call maybe some vagueness around that, maybe sometimes in our group we call this kind of narrative incoherence, I think, meaning maybe a flag, a signpost for some trauma, obviously. She moved to Canada at 11 with her dad, who works in university administration. And her brother described a bit of parentification growing up, kind of taking a bit of the role of her mom. She had two mild TBIs with no loss of consciousness, an estimated duration of post-traumatic amnesia less than two minutes, no persistent sequelae. In the context of competitive field hockey, which she took up and this occurred at 15 and 17, didn't really give them much thought until more recently when she started to wonder about her cognition. Completed high school, three years of undergraduate degree in university, partly because her father worked in administration and so she had a much reduced tuition. Worked in a number of office jobs, started about a year ago kind of doing some college courses, night courses to train as a financial advisor while she continued to work. She lives with a partner of four years. He works in finance. He's very supportive. They're thinking of starting a family. In terms of her previous psychiatric history, she was treated in her 20s for depression and panic at her family health team with sertraline and CBT from a social worker. These symptoms, the depression and panic disorder, developed in the context of a lot of stress with her academics. And she was also attempting to get her driver's license at the behest of her then partner. She didn't miss any work or school because of this. She achieved complete remission. She actually did her driving test and passed it. Later, someone added seroquil or quetiapine for insomnia in the context of university exams. She doesn't like it very much. She doesn't really take it that often, although it's notwithstanding the way that it's prescribed. Three months ago, she started to develop these concerns about her memory. Describes it very vividly. It was their anniversary, an important anniversary for her and her partner. And she wanted it to be really special. She got a movie, made a really special dinner. The movie was Wolf of Wall Street. She describes the dinner at length, the setup of her partner coming, and her becoming quite distressed because she didn't remember what actually happened in the movie. I've seen that movie. I don't know how coherent it was in any case. But whatever. But this was the trigger. And in my editorializing, this kind of triggered a cascade of worries about her memory. And she started to doubt herself. And she started to struggle more in school and not study the way she used to. It's like she's trying in a different way. When I talk about some of the models at the end, I'll talk about some effortful cognitive functioning versus automatic. So she started to do it in a kind of different way, trying to type notes, setting up lots of timers, extensive calendar for her day-to-day activities. She picked up some of these tips online when she was reading about memory problems and developing dementia later in life. How can you help yourself? Make a schedule. Use calendars. Her schedule was pretty extensive. It had her lunch, and brushing her teeth, and all of this. And it was quite overwhelming. She wondered, is this related to my brain injuries? She was not overly distressed with, I have dementia. But it was something that crossed her mind. And she asked, is this related to my brain injuries? This is something, obviously, that's in the media quite a bit and in the press. She did her MOCA at the family health team. And it was 14 out of 30, which is pretty worrisome. This is certainly in a dementia range. Family doctor arranged for an MRI of her brain, did normal blood work, regular blood work, so CBC, lights, BUN, creatinine, LFTs, beta HCG, TSH, B12, all of that was normal. And she actually had detailed neuropsychological testing that she paid for herself because she was quite worried. This runs in the order of thousands of dollars. It's not covered by our healthcare plan, our health benefits in Canada, or in most places, as I understand. And she's referred to us. I saw her virtually. So she presented to the appointment on time. She was by herself. I later invited her partner to give me a bit of history. He was in a different room. She described, as I said, the details around the date and the whole sequence of events around the onset of her difficulties. She described a feeling of what she referred to as brain fog, just kind of feeling cloudy. Things were more effortful, misplacing things, forgetting what she was doing, losing track of conversations midway through, forgetting a password for her Netflix account, having difficulty retaining what she was reading for school. She spoke about her head injuries, as I said. No family history of early dementia. Her father had a stroke six months ago, and he had cognitive sequelae. She did not put this together in any way at the time that we met the first time. Intact ADLs and IDLs, but she stopped driving. We can recall her mother died in a motor vehicle collision. She herself had anxiety around getting her driver's license. A basic sort of symptom screen, not seeing her as someone who meets criteria for major depression, generalized anxiety disorder, PTSD, bipolar disorder, OCD, although there's some perfectionistic traits, eating disorder, psychosis screen. I'll say a little bit about panic in a bit. No childhood ADHD symptoms or learning disability, kind of chronic intermittent initial insomnia for which she occasionally used this seroquel with some reluctance. Didn't drink much, didn't smoke very much cannabis or use very many cannabinoids, no other recreational drugs. The anxiety was circumscribed around her cognition, and she said she's not worried about her memory, she's worried because of her memory. And this is often a thing where we'll see a patient with functional symptoms and we'll ask them about their mood, and they'll be very specific about saying, yes, I'm depressed. I feel awful because of my symptoms, and they want to be very clear about that, so that's fine. There were some subsyndromal panic symptoms around cognitively demanding tasks that Louise also went to pains to say, these aren't like my panic attacks that I had before. I mention this because this is an interesting thing that we sometimes see in people with non-epileptic seizures also are some kind of somatic symptoms if you walk through the actual incidents and events, they can describe somatic symptoms that fit with anxiety, but often without the subjective feeling of anxiety that they endorse. I mentioned she had some perfectionistic traits. I repeated, I was seeing her virtually, so I don't have like these fancy setups for doing special exams virtually. I just checked her orientation, simple attention, repetition, five-item recall, got her to draw a clock, totally normal. How do we understand her earlier mocha? She was really stressed and anxious at the time that she took it. It was in a busy waiting room. It was just sort of given to her by a student. There were like these plexiglass barriers between the chairs in the waiting room. She was really hot and it just didn't feel, it was not a valid thing. And I mentioned this partly because with some of these patients, if you're going to do cognitive screening, it's useful to do it yourself and actually watch them and do it with them. A really good neuropsychologist will always include a big paragraph, if not a page, on behavioral observations. What does the patient look like when they're doing these tests? Look at things like effort, or did they just give up? Those sorts of things. So collateral from... Roughly three months, approximately. So collateral from her partner, he described her as someone who does things for everyone and is always running around, is extremely busy, if not with her work, her school, her volunteer work with her church, and caregiving to her father where she's going, trying to go for multiple meals a day, arranging various therapies, all of this. No falls or motor symptoms or, you know, apathy or loss of empathy. I'm getting at possible signs of like an early dementia or FTD type picture. Compulsive behaviors, except for the post-it notes and the schedules. And the partner wasn't concerned about her cognition. So I sort of felt like I know where this is going. I'm reassured by this MOCA. I think I know what's happening. And the clincher was, towards the end, I remembered, oh yeah, she just had this neuropsych testing. Obviously I want to look at that. And she said, oh actually I have a copy. And I said, can you send it over? And while we were talking in the appointment, she logged on to her Dropbox, uploaded the neuropsych report to her email, copied my email as we were talking, and sent it over to me. So I'll come back to this in a minute, because this to me was like very important. So what do we think about her diagnosis? Does she have panic disorder? There's some sub-syndromal panic symptoms. She has a history of panic disorder. She has some treatment. Maybe they're in partial remission. Doesn't reflect her experience. She says, no, it's not like that. This is not it. Illness anxiety disorder, I think, is an important consideration. But that, really, there is much more of a preoccupation with having dementia than with, you know, the symptoms themselves. And she may not have any symptoms. She's focused on the symptoms. And then this unsatisfactory, unspecified anxiety disorder. I'm sure we can think of other boxes to fit her in. I would propose, and, you know, part of what we want to talk about today is, you know, could she fit into this notion of functional neurological disorder? So this is the DSM-5 criteria. In DSM-5, as in this may be very basic, or you may not have heard this, it's still called conversion disorder. It's called functional neurological symptom disorder. Most people in the field tend to call it functional neurological disorder, or FND. This refers to one or more symptoms of altered voluntary motor sensory function. Clinical findings provide evidence of incompatibility between the symptom and a recognized neurological or medical condition. It's not better explained by another medical or mental disorder. Causes significant distress and impairment, etc. Big change from DSM-4-TR in the following ways. Number one, DSM-4-TR said there has to be a psychological stressor. The stressor has now been relegated to a specifier. Number two, DSM-4-TR said that to meet criteria for conversion disorder, the psychiatrist, or I guess the evaluator or whatever, the clinician, has to judge that the symptom is not intentionally produced or feigned, which is like impossible. I mean, anyone can fake anything. We're not mind readers. We're not, this is like, so I think the effect of those two things had a really negative influence on functional neurological disorder in the past, in that neurologists would be, were the ones seeing the patients. They would be afraid to make the diagnosis because they would say, I don't know if there's a stressor. Is this a big enough stressor? Did it happen at this time? And I can't tell if they're faking or not. They would refer them to psychiatrists. If the patient would go to a psychiatrist, often they wouldn't and they felt dismissed by the neurologist. And if they actually got in there, then we as psychiatrists would get a little bit worried. Are we missing something? Is there another neurological thing here? We don't know the nuances of necessarily the assessment that was done and the neurologist's thinking. And the patients would really get lost in the shuffle. So these changes, at least from my experience, have really resulted in a fairly profound change. And in our acute care hospital, we are now seeing FND, or functional neurological disorder, pretty much on a weekly basis, diagnosed in, by neurology with collaboration from psychiatry. Whereas in the past, in an acute care hospital, you might see it once a year. Again, this is just my subjective experience. Key thing is this incompatibility. And I want to speak a bit more about that. DSM-5 kind of leaves us in a bit of a no-man's land because it gives us specifiers for subtypes, but it doesn't give us a specifier for cognitive symptoms. This is like a bit of an omission. Most people, honestly, clinicians who work in this area, neurologists and psychiatrists and neuropsychiatrists, are just calling it functional cognitive disorder now. ICD-11 does give that possibility. They call it dissociative neurological symptom disorder with cognitive symptoms. So impaired cognitive performance in memory, language, or other cognitive domains that is internally inconsistent, so we'll talk more about this, and not consistent with a recognized disease of the nervous system, etc., etc. So just to highlight, this is a small issue I think with DSM-5. This was a very influential 2020 paper published in Brain by really a who's who of people in the functional cognitive disorder field, including John Stone and Alan Carson. Earlier in 2015, Dr. Stone had published a paper in the Journal of Alzheimer's Disease talking about functional cognitive problems, perspectives from the neurology clinic, and Dr. Stone had said at that point, I don't think we can propose any diagnostic criteria. It's too early. We don't understand this population. We don't know anything really about them. By 2020, they had proposed some diagnostic criteria, and as you can see in box two on the right side of the screen, it's essentially consistent with the way that functional neurological disorder is defined in the DSM-5 and in ICD-11, so one or more symptoms of impaired cognitive function as opposed to voluntary motor sensory function, clinical evidence of internal inconsistency, not better explained by another medical or psychiatric disorder, and caused distress or impairment. They didn't put as a specifier the stressor, which on reflection, you know, may be kind of too bad, but in any case, these are kind of their proposed diagnostic criteria. So what do we mean by internal inconsistency? It's in the DSM-5 criteria for functional neurological disorder, and it's in these proposed functional cognitive disorder criteria. Internal inconsistency refers to examination of a particular function in one way, and then elicit where it may be deficient, but then eliciting that function when you examine it another way. So Hoover's sign is the is the classical one, and you know, I was at a CL master class here at the APA a couple days ago, and David Perez asked who knows how to examine for Hoover's sign, and the whole room of psychiatrists put their hand up, so you you may be familiar with this. So Hoover's sign is a something that you can evaluate in potential functional lower leg, lower limb weakness. So in it, again, you can put your hand under your patient's thigh and ask them to push down on the weak side. They won't be able to. Keep your hand there and then ask them to push up on the other side, and you'll feel it contract on the on the side with the deficit. Hoover's sign is just one example. There's a whole list of these tests. There's a whole world of neurologists trying to test the sensitivity and specificity of these. I did put a note at the bottom, from our perspective as psychiatrists who may or may not examine your patients, I would never take this sign in isolation as being particularly meaningful. This is in the context of a whole neurological assessment, but it does have some utility. So these things like Hoover's sign used to be kind of tricks, tricks of the trade in neurology. So staff neurologists would pass it on from generation to generation by word of mouth. It wasn't usually often in textbooks of this is how you catch your patient with hysteria. The world has totally changed now in terms of the approach of neurology to this. They are now, and I think it's amazing, being completely transparent about this and actually using it as treatment. So when they say, I'm not worried, when they give them a diagnosis of functional neurological disorder, they're showing Hoover's sign and they're saying, see the signal is not getting through when we do it this way, but when we test it this other way, it can get through. There's various metaphors they use. Software problem versus hardware problem. You may have heard that one. They use that a lot and patients really, for some people, it really works. It's a way to show them and they say, this is why I'm not worried that there's a structural lesion in your brain or your spinal cord or your nervous system. This is a functional problem. So they use these tricks now as a type of treatment. So demonstration as treatment in functional neurological disorder. When I get referrals from neurologists now about functional neurological disorder, I want to know all the details of what they've told the patient, what positive signs they've elicited, how did the patient respond. That can often be quite helpful. So what about internal inconsistency in functional cognitive disorder? I gave the example of our friend, our patient Louisa, who was presenting with a MOCA of 14 but was able to do a very complex cognitive task while in the midst of the interview as a potential signpost of internal inconsistency. Ball et al., in the earlier brain paper I mentioned, I'm only gonna, I don't think I have a pointer here, oh maybe I do, only gonna, oh sorry, okay, so really just gonna point to the this portion here. So they say that positive evidence of cognitive internal inconsistency can be demonstrated through any of the following. Any where subjectively reported cognitive difficulties and our low standardized cognitive test results directly contrast with conversational abilities observed in the interview. So Louisa gave us like this very detailed description of the onset of her cognitive problems. Reported activities such as being involved in a cognitively demanding occupation or difficulties only occurring in certain situations. So very typically it's at work that it may be happening, less so in other contexts. So these are proposed as, you know, potential evidence or signposts for inconsistency. And collateral history suggesting that the concern is higher in the individual than their supporter. So I mentioned that Louisa attended alone. There's actually been a number of papers published and they call this attending alone sign in the context of a cognitive clinic. And also part two here, specific patterns if you have neuropsych testing that indicate the cognitive processes perform better when they're accessed with a different test. Neuropsychologists have a huge toolbox of tests they can apply to often test similar functions in a different way. So that can be quite helpful. I'm just looking at my time and I'm talking way too slow. So what are candidate positive features of functional cognitive disorder? So I mentioned attending alone. This is from a McWhorter from the same group of Stone and Carson. This was a lovely paper, a systematic review of literature and some candidate positive features. Attending alone. They're contrasting this with degenerative brain disease, of course, which is what we or they don't want to miss. The patient is more aware of their problems than other people. That's why informant interview in any cognitive assessment is key. They answer independently. Normally if I'm interviewing someone who has a neurodegenerative disorder they'll often, though not always, defer to their family or whoever's with them. They call this the head turn sign. Detailed description of complaints. Sometimes they'll have it all written out and dated. Sometimes it won't be incredibly organized. The people with dementia tend to not be able to describe a lot of their symptoms. In fact, most of the time they're quite unaware of it. They frequently offer elaboration in detail. They can answer questions with multiple components. So I've tried to, when I'm seeing such patients, be cognizant of this in terms of how I ask questions and seeing what they can get if you ask a sort of complex type of question. People with functional cognitive disorders, McWhorter et al., propose can give a detailed account of their personal history, drugs, previous interactions with doctors. I've asterisked this because I think for those of us who work in psychiatry with people who have a lot of trauma histories, we know that sometimes the narratives can become a bit disjointed around things that are traumatic. Sometimes in people with functional disorders, the traumatic things have been their encounters with other doctors. Normally people with dementia don't lose autobiographical memories until later in the disease process. Functional cognitive disorders, people may complain about memory gaps for specific periods. So Louisa's case, she doesn't really remember the period after her mom died. It's all very vague. People's symptoms can sometimes be within normal experience and the patient will say, you know, I forgot my PIN number and they're devastated. And you're thinking, I forget my PIN number all the time. Approximate answers. So this is an interesting sign relating to something that used to be called Ganser syndrome. But that's where, you know, you say what's 2 plus 2 and the patient says 5. Or they give an answer that's close, suggesting that the correct answer is somewhere in there. Also dating the symptom onset with precision is considered a possible candidate positive feature. Unstable longitudinal course, and marked variability. Whereas in degenerative brain disease, the cognitive impairments progress, are progressive. So they get worse over time and there's, you know, less variability. There's exceptions, of course. You know, things fluctuate. Dementia with Lewy bodies has fluctuations. Parkinson's related diseases have fluctuations. Deliriums, of course, have fluctuations. So how does this work? How do we, how do functional cognitive symptoms happen? This is very, very speculative, but there have been some really, some really elegant work done by various neuropsychology and neuropsychiatry research groups. One pathway here is metacognition. Metacognition is really thinking about thinking. It refers to our ability to reflect on and monitor our own cognitive processes. It's been proposed that individuals with functional cognitive symptoms may have a deficit in that. So on some specific specialized tests, they perform accurately on what is called local metacognition. Local metacognition is minute-to-minute task focus measures, whereas a more, more long-run self-evaluations of their performance, termed global metacognition, is felt to be inaccurate. The authors speculate that this disconnect leads to the disconnect between impaired global metacognition and intact local metacognition leads to this experience of cognitive symptoms. Do you have a simple example of that? Of metacognition? Of the impaired one, of the impaired global? Yeah, so impaired global, so local would be if you give me a test of, let's say, my attention. Let's say you give me a digit span test. And I do fine. And I say, yeah, I did fine. But I still have trouble with my attention. And I think it's a more broad reflection of the person's abilities. That said, these are very specific tasks that they did. And I don't recall off the top of my head what they actually did to differentiate local versus global. But that's a great question. Attention has been perpetually evoked in functional neurological disorder. I'm getting a bit tight on time. But I am just going to note that excessive or misdirected attention internally is thought to be one potential mechanism, leaving less attentional reserve for other things, slower information processing. Other aspects are, Adriano mentioned, memory perfectionism, so this unrealistic expectation of how my memory should be and kind of over-interpreting cognitive failures. And then a heightened degree of monitoring my memory. How am I doing? How am I doing that's actually taking away from my doing the task? So again, these are very speculative. Treatments are far less studied than in other FNDs. I would say in other FNDs, the status of treatment is in the mature preliminary stage. So if you have motor symptoms, physio. If you have non-epileptic seizures, cognitive behavioral therapy can be very helpful. And there's a number of groups working on this. So we essentially try to use those same principles in functional cognitive disorder, really tailoring the treatment to the patient formulation. Neurosymptoms.org is a fabulous website. If you don't know it and you see these patients and there's one thing you could do, this would be it. Show it to your patients, look at it with them. This is developed by Dr. John Stone, University of Edinburgh. Adriana just showed me they have a new app where you can put your own symptoms in. I've had only positive experiences with patients looking at this. It really helps them to feel validated. It's written by neurologists. Very nice, and it's often updated as well. So how can you contextualize their symptoms? You can give them a little piece, a little chunk of sort of, I can't call this psychoeducation. I don't know if that's the right word. But talk about how we need our attention to be intact in order to be able to encode and recall information. Sometimes when we go into autopilot, let's say I'm driving to work and don't remember what happened, that's actually a normal and adaptive way for our brains to conserve attentional resources. Patients may over-interpret those. Like, I came here and I don't remember how I got here. I know I drove. So trying to kind of reframe it a little bit. Help them to identify areas where their cognition is intact, if there are inconsistencies between different settings. Make sure, obviously, we have to address their worries and concerns. If they're worried this is due to a TBI or if it's due to a neurodegenerative disorder, be honest and transparent about why you think it's not. And if that's something that you feel is within your scope, if you don't feel it's within your scope, then convince yourself. Talk to their neurologist and then explain it to them. That would be my suggestion. And obviously, address issues around CNS hyperarousal, and which really makes it difficult to do anything productive except maybe flee from danger. Again, this is just a overview of addressing other symptoms. Pain, shortness of breath, fatigue, that sort of thing, environmental factors. We're moving towards a kind of supportive, educational approach here, identifying all the factors. I mentioned Louisa was doing everything for everybody. There's been a lot written about FND with women being overrepresented. There's a lovely paper in JNNP framing FND as a feminist issue. I say this all to come to household tasks and divisions of responsibilities and things like that, in that women often will have inordinate caregiving roles and what my wife calls emotional labor. And sometimes trying to address that in some way can be helpful. Look at medications, see if there's things you need to get rid of if the person is feeling too tired, things like apopentin, Seroquel, quetiapine that people may be on that may not be helpful or indicated. Optimize comorbidities. I'm always looking out for people who maybe should have a sleep study. Addressing the ways in which they try to compensate with their notes and alerts and reminders and just attending to this if it's an issue. Use a sort of cognitive approach to try to understand if there's some catastrophic thoughts or automatic thoughts. Again, potential foci of treatment. And I do encourage people to not avoid cognitively challenging tasks in the same way that Adriano probably encourages individuals with mild TBI to not abstain from activity and stay in a dark room. That's probably not helpful. So what of the future? What can we think about? I know our time is very short, so we know that subjective cognitive symptoms are very common in the general population. Some of these people are going to primary care or memory clinics. About 70% of people going to memory clinics with subjective cognitive complaints don't have dementia. That figure, I'm sure some will argue with. It may depend on the center, but I'm quoting the literature. 12% to 56% of new referrals to tertiary memory clinics have functional cognitive disorder. I don't know what's happening with these people. What is their outcome? What is their profile? I think it's important to identify these people. Number one, if you're going to be doing treatment and biomarker trials for Alzheimer's disease, you might want to have this subgroup excluded. Number two, I think, and Stone makes this argument, we can really cause iatrogenic harm if our patients think they have a neurodegenerative disorder when that may not really be the case. So we ought to be careful and thoughtful about it. Finally, there's a whole slew of biomarkers in research and maybe in your centers in clinical application, amyloid, tau, various CSF biomarkers, PETs, different types of MRI. As these biomarkers take shape, is it going to create a population of people who become preoccupied with their cognitive function, who have no complaints if they test biomarker positive? The current dominant model of degenerative disease and memory particularly in the memory clinic has in some ways considered subjective cognitive impairment as a precursor to MCI, as a precursor to dementia. This really neglects a huge chunk of people who do not get dementia. A newer model proposed is one where we kind of consider all these factors as largely separate, potentially overlapping. OK, this is a summary. It's actually very similar to what I said when I summarized Adriano in David's work. Thank you so much. I'm so sorry that we went over time. We are here for questions. At least I am, as long as anyone wants to talk. If anyone wants to talk. Yeah, so my name is Barry Reisberg. And I do want to add a very brief historical context here. So we, in 1982, Reisberg, Ferris de Leon, and someone named Thomas Crook, published in the American Journal of Psychiatry the evolution of dementia. And we identified seven major stages in that evolution. And first, of course, is normality. But in persons as they age, as they progress, go on to a stage of subjective cognitive, what we now call subjective cognitive impairment, or subjective cognitive decline. In otherwise healthy persons, and this is the part that's most relevant here, these people complain most prominently of not recalling names as well as they formerly could. And the next most common complaint is not recalling where they placed things as well as they formerly could. And we showed in 1982, and in the subsequent years, that this is a stage. And it lasts approximately 15 years prior to an entity, which is also now well-known, for which we coined the term mild cognitive decline or mild cognitive impairment. That's an entity which lasts approximately seven years in otherwise healthy persons, in which subtle overt deficits occur in addition to the subjective deficits. And that seven year stage is followed by the various stages of dementia, which we also described in 1982. So I just wanted to add this historical note. Well, thank you for that. And I would really love to look at that work. I think the perspective that is advocated here is simply that subjective cognitive complaints are not invariably going to follow a linear progression to MCI and dementia. I think the difference is, again, ruling out other concomitant, what you might call comorbidities. So we studied persons. We carefully excluded persons with other conditions in these studies. Thank you. I have a question. In the account that you gave, I sensed that there are a lot of psychiatrists that put it back virtually. What are your thoughts on that? Do you think you would wait through the psychoeducation and see what happens? And then have it in the back of your head, maybe also put it back on anymore? So I think that's a great thought. And that would be the easier thing to do, in a sense. And I think it would depend. I would not want to. First of all, I would propose increasing the searcher lien, because she is taking it. So she was on 100. And it's an option. And I think it's fair to present it to her. I wouldn't want to try to do either or, though. I think the psychoeducation and some of the pointers that I went through very quickly, I certainly wouldn't want to neglect those. But absolutely, that's a- But the issue would be, I would think, OK, we would not want to include things like that. Include the psychoeducation and see what happens there, as opposed to doing both. But you think either one is an option. Yeah, I mean, I think either one is an option. And I give these options to the patient. And of course, I would say to the patient, I guess a drawback of doing the searcher lien is, if you get better, we're not going to know what did what. But it's up to her. But I would try to, all of that psychoeducation piece, I think, could be done in a fairly brief period of time. Like, it's not extensive work. But you would be responsible if they take time. I would think that she would need to practice it. Absolutely. So I'd take doing that now in a week. But that's how long it's going to work. I would think that we should take the time to have a look. Yeah, absolutely. I want to turn to my colleague, David, who has a lot of experience with, if he has anything to add, with CBT and actually with pharmacotherapy and the combination, and also with a very important thing, well, measurement-based care. I don't know if this fits. So I think that what Dr. Ghaffar is getting at is the value of, I think, incorporating measures into the work when we're tracking these symptoms. And so the value of potentially using a scale, like the perceived deficits questionnaire and routine clinical practice, that you're able to track meaningfully what are their symptoms coming in when they're coming to see you as a doctor or provider, and then integrating your intervention, whether that's including psychoeducation, whether that's including CBT, whether that's including whatever the model might be, and tracking these symptoms as you're going along and being able to use that to help monitor and guide treatment decisions. I know that, yeah. That's exactly what I meant. I mean, just doing it in a sort of systematic way. Yeah, thank you. Thanks so much for the great talk. And it was very helpful to see the kind of possible and emerging standards for internal inconsistencies for the functional neurologic disorder. But they would still seem to me like a little bit more gray than you might have with functional motor disorder. So other than just taking a super detailed history, any tips for ruling out factitious disorder or even secondary gain when someone's presenting with FND? So I agree, it's complicated. And it is, I think that functional cognitive symptoms are maybe a degree more complicated than motor symptoms. The factitious or malingering, again, you know, my thinking has shifted in that over the years in that it's not, A, I feel like I don't see it very much. Now, it depends where you're working. If you're working in a psycholegal setting or you're working, you know, you're doing a lot of independent medical evaluations, it's a very different, it may be a different population. So it is not generally something that I think about in my differential unless there's something glaring or something comes out to me. That's my approach. I don't know if David or Adriano have any comments on factitious and malingering. Any pointers on how to rule them out? I guess one thing is it's, you know, it's hard to rule them out. It's just not something that I feel I've seen that commonly in my experience. And just one setting where I keep thinking about it is in the geriatric population. So sometimes where it's just actually intense depression, anxiety, but now they're complaining of cognitive symptoms where there is a question of like, is this to facilitate getting long-term care placement if they're lacking resources? And that kind of question comes up sometimes, especially in individuals who also have like functional movement disorders concurrently. And so the suspicion starts to kind of come up a little bit, but yeah. So I'll jump in to add the piece around just highlighting, because this question, I think, can emerge when we're talking about functional neurological disorder, functional cognitive disorder, certainly shows up in other practices, especially because there is this overlay of this way that different diagnoses can fit into sort of the legal frameworks, ways that people having accommodations, disability, payment, these sort of pieces. I'll highlight just the other nuance to the topic, which I don't know if it directly answers the question, but it sort of just adds more complexity, which is the validating role of these things. Like a lot, I'll give the example, a lot of patients may come to an MS clinic concerned about the impact of their symptoms on work and whatnot. And it can be a very long and difficult process to actually end up getting disability or getting payments or accommodations or whatnot. And so there is a, I think, although we often think of it in the context of like malingering or something which I think implies this notion of like nefarious intent, there is an aspect to it that is also very validating to get, to have long-term disability, to have accommodations in a way that it can be very validating. And I think, so I don't think it directly answers the question, but I think it highlights that it's not, that there's different ways that these factors can play a role without the person necessarily having conscious or unconscious awareness per se. Thank you. And of course, just to point out, which we said already, and I know everyone knows, is that necessity of excluding factitious disorder in malingering is removed from the criteria in DSM-5. I'll also just note that most people that we see in downtown Toronto don't want to go to long-term care. Thanks for the talk. I found it really interesting. I see a lot of this, but just in different contexts. Mostly, my friends who are in their 40s, all of us have it with our caregiving responsibilities. But in my practice, I see it in women who have babies in their 40s, perimenopause. Obviously, it's really common. And just in my general population. But I guess where I am concerned is where I also see this kind of idea is people in their late 50s or 60s, who are very intelligent. And obviously, neuropsychological testing, I think, is rubbish for intelligent people. Because when you see them over time, people think, no, they don't have early dementia. They obviously do. It's just they're really intelligent, and they're able to compensate. And so I think people get brushed off as having this, when they actually do have early dementia, or developing dementia, but they have excellent compensatory mechanisms. For instance, they can be still operating as a university or college professor. I think you call it here. A college professor, and within a year, end up in a nursing home, because they have managed to compensate because of their excellent intelligence. So I think one of the difficulties is intelligent people who compensate. I just wonder if you could comment on that. Also physicians. Yes. And yeah, that's it as well. And also, when you see them, and you're concerned about their capacity, actually, to operate as physicians. But they have fabulous communication and compensatory styles. And it's very hard to get them to admit what's happening. Or when they come to you, and they actually look like the FND, because they have notes. They have the exact occurrences where it happens. But they're actually just smart, and intelligent, and aware. Yeah, I mean, I agree. This is very difficult. There's no, if someone is performing normally on cognitive screening, or neuropsychological testing, and they are continuing to function in their usual capacity, but there are subtleties that are kind of noticed. I guess one question is, to what degree does it distress them? And does it distress them at all? In this population, I think that I'm talking about, that we're talking about, are people who are more distressed by it. So is your college professor worried about his or her memory? Oh, yeah, I've seen a few of them. And they're very worried about it, but people telling them it's normal. But then when you follow them over years, it's definitely not. And they deteriorate in a typical dementia pattern. It's just that it's like they suddenly fall off a ledge, that they manage to compensate. So past tests look like they're just, I don't know, like just a functional disorder, but it's not. So one of the things I'll also highlight is in the MS population, I know that they're now advocating in the guidelines from the MS Society. I think of Canada. I have to double check which specific society. But for baseline cognitive testing in this population, I think to capture some of what you're describing, where there's people that, according to normative data, test normal, but there are these subtle changes in cognition because they were so high performing or had such a high level of pre-morbid functioning. And without that prior cognitive testing, it can be really tricky to sort out, is this a change? Is this not a change? It's hard to know. And so I- Yeah, because they could do 20 numbers at the start, and then they can only do eight after time or something. Yeah. It's really challenging, what you bring up. But I guess the other thing I'll put out is, is it necessarily a degenerative brain disease? Oh, it's clear after time that it is. So I guess there's the ones who come to me now who I don't know, and the ones who I've followed up over 10 years who I now know. It's become very clear after time. Because you had mentioned kind of menopausal influences and things like that. And some of those you don't know. It's only time will tell. Yeah. Yeah. OK. Thank you. Actually, one thing on that is, so with functional cognitive disorders and in the broader world of functional neurological disorders, we're still in the relatively early stages of really understanding what's going on across all subsets. But at the end of the day, I mean, it's a neurological condition. It does affect the brain. And Alberto Espe in Ohio is doing some interesting work identifying- he's identified a subset of functional motor disorder that is a harbinger of Parkinson's disease. And so, I mean, even within this realm of what we call FND, it's not that- I guess it's sometimes even tied into this notion of fainting or things will get better. It's not that. We're still trying to identify what this condition is. And as we understand it better, we can start identifying, perhaps, these other patient groups that either fit into it or don't. Or maybe it's a harbinger of something else. We don't really know. But it's an excellent question. So thank you for bringing that up. Thanks. So I had a question in terms of the clinical setting. So, of course, after validating the patient and trying to check all the boxes in terms of kind of addressing their concerns, do you have any advice in terms of dealing with patients who are very resistant to our attempts at educating them and explaining what we think is going on? Yes, I think that's a great question as well and very clinically relevant. I think at the end of the day, we have to meet patients where they're at. And it's important to say that my job as a clinician- and things might work differently depending on the system that you're in and the context you're operating in- but I think it's important to be transparent about my intentions is just to deliver what it is that I think based on these signs and leaving the door open to them, to just opening up a conversation with them. But to say that it's not- if there's a lot of resistance, and particularly in the FND world, if there's somebody who's very focused on wanting ongoing medical testing, they're not really aligned with your perspective, then that's okay. I think there's just some- you have to pick and choose your battles. And in some patients, I don't know if it would be fruitful to really heavily argue against that. And I think there might be some damage to your trust and alignment, but I think it's important to keep a door open as well and for having them see themselves. That's one perspective. Okay, thank you. Thanks. Hello, thanks for the talk. I had two questions, if I may. One of them was related to an early question about if there's any tips on how to try and differentiate these populations better. What's your thoughts on the role of performance validity testing in the role of internal inconsistencies? So it's an interesting area, performance validity testing. I know they have these measures out there. There's a test of malingering. There are these validity testing. And I'm trying to remember- I don't have the resource, but they did look at this for the MoCA in the TBI population. It's a paper that came out in 2019. And I'm blanking on the author's name. Apologies, but I'm sure if you look that up, validity testing using MoCA in the concussion population 2019, you'll find the paper. But I think as well, it kind of depends, as Dr. Ghaffar said, on the clinical context that you're working in. So something like that might be more relevant if you're working with insurance assessments or independent assessments to really suss that out. You probably should be working with a neuropsychologist who- or if you don't have the expertise, somebody who has the expertise to deliver that intervention and- or sorry, that test and interpret those results. But we know that effort will influence the testing results, like the cognitive test results. So it's an important area. Thanks. And sorry, just one last question. Do you think that there is any relationship between the adults presenting for ADHD-type symptoms, if there's any association with that and functional cognitive disorders? So I don't know. I don't even- I haven't seen a paper on that specifically, but I've quite literally in the last few weeks seen someone or in a couple of people presenting with specifically that concern of, do I have ADHD? And it actually reflecting in an MS center emerging cognitive concerns. So I don't know if there's any literature out there on that piece, but it's something that is showing up in clinical practice. I think probably we- I don't know the literature on this, but certainly anecdotally and what we've heard from others is, you know, there's really been an explosion, particularly, I think, since the pandemic, especially around ADHD. So we will get people in a rehab hospital who are referred after an accident, and they'll say, oh, I think I have ADHD, by the way. So these are now coming as CL consults. So certainly something that we're seeing in a non-functional cognitive disorder setting. And we don't- none of us work in a specialized functional cognitive disorder setting. But I think that's going to be a part of the differential and a part of why some people maybe are presenting also. My question or reflection is, has there been any discussion over how this relates to burnout? Because the case presentation you presented sounds like a very typical burnout patient or burnout situation. And this feels like a very helpful framework to discuss how burnout can affect cognitive symptoms. Has there been any discussion of this? I'm glad you find it a helpful framework. And that was our hope, is that this would be kind of an overarching, helpful framework. With respect to burnout in particular, I haven't, but I don't know if my colleagues have. I'd seen this, I'd heard about this more. So not in literature, but I'd heard about this in a talk as well. Someone had similarly made a link in that respect. And they actually connected it back to this concept of epiphenomena in psychiatry and in, I think, the history of psychiatry. And I think that even ties a little bit back into that concept of neurasthenia that emerged previously. And I even wondered, actually, as you bring this question up, in the previous question around these query around ADHD assessments, if that even, it's hard to always tell when you're in the midst of what is an epiphenomenon and what's going on, but whether or not, in some ways, balancing that with greater awareness and recognition of ADHD and those aspects. Also wondering where burnout fits as an epiphenomena, where neurasthenia fits as an epiphenomena. Are we capturing something? Does the label of functional cognitive disorder, like, are these things that are trends in psychiatry and things that ebb and flow? But hopefully, that functional cognitive disorder captures something that is more constant or more consistent that just keeps emerging with different labels or different names. But I'm not aware of literature, but I've heard other people make a link in that context. Yeah. Because in Sweden, where I'm from, we have a diagnosis, which is basically burnout syndrome. Oh. And how this is, exactly how we say, if this is what's underlying of all these diagnoses that have been appearing over time, is this what we're actually seeing? So that's interesting. I think that would fit into the broader realm. When we're doing an assessment, we think about predisposing, precipitating, perpetuating factors. We try to have a biopsychosocial approach. So if there are certain stressors that are perpetuating the condition, I mean, the brain's going to respond and adapt and change to whatever's going on in the environment. And to some degree, it's happened on a massive scale, given the pandemic and other global issues. But I think if you're thinking about that, if it's relevant, if it seems relevant for the person in front of you, then it's going to be an important thing to try and flesh out and address. And I think it's a false distinction to think that because there's stress in your life, that doesn't affect you biologically, or that it doesn't affect your brain and how your brain works. I think that's a false dichotomy that we should probably be moving away from. So it's just important to assess and capture. I wanted to thank you for this, because I work at a VA. And one of the most common things I see are people that have had blast injuries, TBIs, mild TBIs. Most of these young men, however, are still complaining about some of the same things your patients complain of. But in addition, they have PTSD. And trying to ferret that out is near next to impossible. The evaluations that are done in the VA for TBIs, in my opinion, are worthless. Because they all say, well, it's because he has PTSD that he has these symptoms. And it's very difficult. Because trying to educate, some of this is your PTSD, your hyperarousal, which makes you anxious, which makes you not pay attention to what you're doing. So you forget about what you're doing. It's helpful. But at the same time, they're saying, yeah, but I can't do what I'm supposed to do. I have utilized stimulants a lot. My patients tell me they swear, if I don't take my medication, I really can't function. So I'm assuming it's helpful. But I really appreciate hearing what you said. Because as a psychiatrist in the VA system, we're told that the TBIs are just forget about it, that's not an issue. But I really think they are. And hearing you say what you said, that they do notice the cognitive differences and complain about them, and us saying, well, don't worry about it, that doesn't work. So I really, really appreciated what you said. Thank you. Hi. Hello. Looking at your physiopathology that you proposed about metacognition, I thought that can we get better results with antidepressants that increase frontal activity, like Vortioxetine, Vopropion, SNRIs? And have you used those kind, and what's your results with that kind of patients? Certainly I use, I mean, it's an interesting hypothesis. And I guess stimulants also can fit with that a little bit. I'm not aware of any evidence around that. And in my clinical practice, I don't know that I, just trying to think about specific cases, I mean, obviously we will select an agent partially based on, you know, obviously previous experience and tolerability and the symptom target. So I think in some way, yeah, I do kind of do that, not in a systematic way. I think in the way that you're suggesting. I don't know if you guys have any comments. Well, just, it's an interesting question to think, like, can medications help with metacognition? Yes. How we think about our own cognition and brain. And I don't know, like, this is sort of a, it feels like metacognition. I'm sure it's been, you know, out there and studied for a while, but it's probably just more recently emerging as a thing. And I guarantee, like, probably in any pharmacology study, it's not been looked at or considered. So we probably don't know. But what I would imagine is that if there is something that you're trying to target with your pharmacology, if there's, like, comorbid depression, if there's comorbid, like, other concerns, probably it's going to free up the brain's resources to actually be able to think better about oneself. And maybe those are interventions better targeted by psychotherapy. But I don't know. That's a really interesting, like, gap and point. Thank you. Hi there. Thank you for an excellent talk. Just had a question about, it sounds like part of the possible pathophysiology would be around attentional reserve. Just wondering if you've come across any studies or even anecdotal stories about mindfulness for this population as a way to kind of target attention? So, yes, is the short answer. It's just that these are, like, pilot studies. They're small. Acceptance and commitment therapy is sort of another, like, avenue that's being explored and looked at in the FND population. But with functional cognitive disorder specifically, I mean, there's just such a lack of available treatment, anything, right now. So, like, theoretically, though, yeah, I think there's good rationale for using mindfulness. And, I mean, ultimately, we have to, it's probably good to offer something to our patients. And I think that would be a reasonable thing to offer someone. So we're using mindfulness through one of our CL, psychiatry advanced practice nurses, for many populations in our sort of referral pool, including those with functional symptoms. And certainly anecdotes where the patients have found that tremendously helpful. But I think, like Adriano said, I think in FND, there are some pilot studies and case series. But nothing, you know, really definitive or systematic. But day to day, I mean, we say we're always referring to Mary, our advanced practice nurse, who does this kind of mindfulness coaching or training in just one or two sessions with patients. And, you know, it's been, you know, remarkably helpful. So just seeing no more questions, thank you all for staying. I know we have gone a fair bit over, but we're all still here. If anyone's interested in speaking or coming up, it's been a pleasure to give this talk. Thank you.

subjective cognitive impairment

neuropsychiatry

multiple sclerosis

mild traumatic brain injury

functional cognitive disorders

mood disorders

psychosocial stress

cognitive rehabilitation

supportive therapy

post-concussive syndrome

functional neurological disorder

neurodegenerative disorders

emerging therapies

tailored patient treatment

psychoeducation