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Clinical Approach to the Differential Diagnosis Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric Disorders

2015; American Psychiatric Association; Volume: 172; Issue: 9 Linguagem: Inglês

10.1176/appi.ajp.2015.14101248

1535-7228

Simon Ducharme, Bruce H. Price, Mykol Larvie, Darin D. Dougherty, Bradford C. Dickerson,

Obsessive-Compulsive Spectrum Disorders

Back to table of contents Previous article Next article PerspectivesFull AccessClinical Approach to the Differential Diagnosis Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric DisordersSimon Ducharme, M.D., M.Sc., Bruce H. Price, M.D., Mykol Larvie, M.D., Ph.D., Darin D. Dougherty, M.D., M.Sc., Bradford C. Dickerson, M.D.Simon Ducharme, M.D., M.Sc., Bruce H. Price, M.D., Mykol Larvie, M.D., Ph.D., Darin D. Dougherty, M.D., M.Sc., Bradford C. Dickerson, M.D.Published Online:1 Sep 2015https://doi.org/10.1176/appi.ajp.2015.14101248AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail A middle-aged woman with obsessive-compulsive symptoms with atypical features is seen for a diagnostic neuropsychiatric assessment."Ms. A," a 46-year-old woman, was referred for inpatient treatment at the Obsessive-Compulsive Disorder Institute (OCDI) of McLean Hospital (Belmont, Mass.). She had no prior history of psychiatric disorders. Two years earlier she had developed cleaning and checking rituals that gradually became severe and intrusive to the point of losing her long-term employment. She had been diagnosed with obsessive-compulsive disorder (OCD) by a community psychiatrist. Sertraline was prescribed, but she soon stopped taking it because of side effects. After a few days at the OCDI, a diagnostic neuropsychiatric assessment was requested because of atypical features for OCD, including a late age at onset and an inability to engage in therapy.Ms. A denied obsessions or anxiety. She felt well and had no concerns about having lost her job. Collateral history was obtained from her husband. After the onset of compulsions, he noticed major changes in her personality. Ms. A had previously been caring, organized, and reliable, but over the past 2 years she had become emotionally detached and apathetic, and she now had poor judgment and neglected her daughter. She also exhibited odd eating behaviors, such as eating butter by the spoonful. Most recently she had developed bilateral hand-rubbing stereotypies. There was no family history of psychiatric disorders, dementia, or amyotrophic lateral sclerosis.On examination, the patient was superficially cooperative, but without insight, awareness, or concern about her behavior. Her affect was jovial and shallow. She was indifferent to her family's concerns. There were no psychotic symptoms or language abnormalities. Her score on the Montreal Cognitive Assessment was 25/30 (3/5 in the visuospatial and executive tasks, 4/5 on the serial 7s task, 3/5 on the recall task, +2 words with cues), and her score on the Frontal Assessment Battery was 17/18. On phonemic fluency testing, she listed 12 words, reciting more words in the first 15 seconds than in the last 45 seconds (generation deficit). A brief social cognition battery was administered. She made no mistakes on faux-pas vignettes, but identified only 17/36 emotions on the Reading the Mind in the Eyes test. Her elemental neurological examination was normal except for inextinguishable bilateral palmomental reflexes.While Ms. A's compulsions were typical of OCD, the clinical profile was not compatible with this diagnosis because of the absence of anxiety or distress related to the rituals. Given the history of loss of empathy, apathy, careless actions, dietary changes, hand-rubbing stereotypies, generation deficits, and impaired facial emotion recognition, she met clinical criteria for possible behavioral variant frontotemporal dementia (bvFTD). A recent brain MRI performed at a private facility was reported as normal (images were not available for review). However, another brain MRI, at our hospital, showed moderate to severe circumscribed ventromedial prefrontal and orbitofrontal cortical atrophy bilaterally. A [18F]fluorodeoxyglucose positron emission tomography study demonstrated marked cortical hypometabolism within the medial aspects of the anterior frontal lobes. Hematology, biochemistry, and EEG results were within normal limits. The final diagnosis was probable bvFTD. A genetic evaluation revealed none of the autosomal dominant mutations associated with frontotemporal dementia (C9ORF72, progranulin, and MAPT).Over the next few months, aggressive behaviors at home became more prominent. Divalproex sodium was initiated for behavioral management. Despite the medication, Ms. A's behavior continued to deteriorate, and she was admitted to a psychiatric ward after biting her daughter. She was placed in an assisted-living facility 30 months after the onset of symptoms.Frontotemporal dementia (FTD) describes a heterogeneous group of neurodegenerative diseases featuring various combinations of behavioral changes, language abnormalities, social cognitive impairment, and executive function deficits. FTD is divided into two major clinical syndromes: the behavioral variant (bvFTD) (1) and the language variants referred to as primary progressive aphasias (2).Identifying bvFTD is challenging because symptoms can be subtle in the early stages, and they may combine features that are traditionally within the realm of psychiatry (e.g., personality changes, lack of empathy, compulsions) and others usually seen by neurologists (e.g., aphasia, cognitive impairments). Patients are often first evaluated in general psychiatric settings, and about 50% are initially diagnosed with a primary psychiatric illness (3).Knowledge about FTD has grown exponentially over the past 10 years, and it is crucial for psychiatrists to include bvFTD as part of their differential diagnosis in a wide range of adult psychiatric disorders. In this article, we review the clinical approach to bvFTD, focusing in particular on the differential diagnosis between bvFTD and primary psychiatric disorders.Definitions and Diagnostic CriteriaDiagnostic criteria for bvFTD were last revised in 2011 (1) and are included in DSM-5 (major frontotemporal neurocognitive disorder). A DSM-5 diagnosis of bvFTD requires the insidious onset and gradual progression of a neurocognitive disorder combined with at least three behavioral symptoms and a prominent decline in social cognition and/or executive abilities. Behavioral symptoms include disinhibition, apathy or inertia, loss of sympathy or empathy, perseverative, stereotyped, or compulsive/ritualistic behaviors, and hyperorality and dietary changes (which can lead to weight gain). The clinical phenotype sometimes includes features of the Kluver-Bucy syndrome (e.g., docility, oral exploration of inedible objects) (4). Current diagnostic criteria state that there should be relative sparing of learning and memory and visuospatial (perceptual-motor) function. However, multiple studies have challenged the validity of this criterion by showing significant impairment of memory functions in bvFTD (5, 6) and parietal lobe deficits in FTD due to progranulin (GRN) mutations (7). Consequently, the presence of such deficits should not be viewed as an absolute exclusion criterion in clinical practice (although in research studies they are used in part to exclude patients with atypical Alzheimer's disease). The diagnosis of bvFTD is referred to as possible bvFTD when it is based solely on clinical criteria. Supportive neuroimaging or genetic findings can increase the degree of certainty of the diagnosis (see the Neuroimaging and Genetics sections below).One exclusion criterion is that symptoms should not be better explained by another mental disorder, which is often challenging to determine. In this article, we use the term "primary psychiatric disorder" to describe emotional and behavioral syndromes for which there are no currently identified diagnostic pathology correlates (e.g., major depressive disorder, schizophrenia). We consider bvFTD to be a quintessential neuropsychiatric disease, and we recommend abandoning the false dichotomy of bvFTD being "neurological" as opposed to "psychiatric." In our opinion, conceptualizing bvFTD as not being "psychiatric" because pathological correlates have been identified is neither clinically helpful nor scientifically valid. Both psychiatrists and neurologists need to have basic competence in identifying patients who are potentially suffering from this disease.EpidemiologyThe estimated incidence of FTD is 2.7–4.1 per 100,000 people, and the prevalence is 15–22 per 100,000 (8). There are reports of a higher incidence of bvFTD in males, but overall there is no consistent gender disparity across studies (8). FTD represents about 5% of all cases of dementia in unselected autopsies. Although onset is typically between ages 40 and 70, up to 25% of FTD cases occur after age 65 (8). Late-onset bvFTD is probably underrecognized because of the clinical overlap with Alzheimer's disease (9). Onset as early as the 20s has also been described. The median life expectancy is 7–8 years after the onset of symptoms, but the rate of progression varies significantly among patients (10).PathophysiologybvFTD is characterized by bilateral (often asymmetric) atrophy of the frontal lobes and the anterior temporal lobes, reflecting neuronal loss, microvacuolation, and a variable degree of astrocytic gliosis, referred to as frontotemporal lobar degeneration (11). Neuronal dysfunction is thought to be caused by the accumulation of one of several protein aggregates, including tau, 43-kDa TAR DNA-binding protein (TDP-43), RNA-binding protein fused in sarcoma (FUS), and ubiquitin-positive proteins (11, 12). Most cases of bvFTD are due to tau or TDP-43 (in equal proportion), but a small proportion are caused by FUS or a predominantly frontal variant of Alzheimer's disease (12). Of note, Pick bodies are a specific cellular morphologic subtype of tau accumulation that is not present in all cases. Consequently, "Pick's disease" should no longer be used as a clinical diagnostic term.There are three main causative autosomal dominant genetic mutations with almost complete penetrance: microtubule-associated protein tau (MAPT; 17q21), progranulin (GRN; 17q21), and the recently discovered chromosome 9 hexanucleotide repeat expansion in C9ORF72 (12). MAPT is also related to parkinsonian syndromes, and C9ORF72 to amyotrophic lateral sclerosis (ALS). Approximately 10%−20% of FTD cases have an autosomal dominant inheritance pattern (13, 14); therefore, most cases are sporadic. There are no known replicated nongenetic risk factors (8).Overlap and Differences Between bvFTD and Primary Psychiatric DisordersIn this section, we review the overlap and differences between bvFTD and primary psychiatric disorders in terms of clinical symptomatology. A schematized summary is provided in Figure 1. Differentiating factors in neuroimaging and other biomarkers are covered afterward, in the Clinical Approach section.FIGURE 1. Algorithm to Determine Whether Behavioral Symptoms Are More Compatible With Behavioral Variant Frontotemporal Dementia (bvFTD) or Primary Psychiatric Disordersaa This figure is intended as a guide to determining the most likely diagnosis and should not be interpreted as an absolute division between disorders.Major Depressive DisorderMajor depressive disorder and bvFTD share common symptoms, including lack of interest, decreased motivation, low energy, and impaired concentration. Diagnostic confusion can occur between bvFTD and severe major depression that is causing impaired cognitive processing. However, sustained depressed mood, which is a hallmark of depression, is usually not present in bvFTD. Other symptoms of major depression rarely seen in bvFTD include guilty ruminations, feelings of worthlessness, and suicidal thoughts. Patients with bvFTD sometimes report mood changes (e.g., inability to feel normally), but their descriptions tend to be shallow (15).Major depression can also present with diminished interest or pleasure (anhedonia) without pervasive sadness, which can be difficult to distinguish from apathy. Apathy is a deficit in motivation, manifested by a reduction in self-initiated or environment-responsive goal-directed behaviors, cognitive activity, and emotional responsiveness. A core distinction is that apathy is not experienced as distressing or accompanied by dysphoria.Geriatric major depression can be challenging, as elderly patients tend to have less subjective sadness, more cognitive symptoms, and less insight (16). Strategies to distinguish depression-related cognitive impairment from bvFTD include a structured clinical history (17), social cognition batteries (18), and neuroimaging studies (see the Clinical Approach section).Bipolar DisorderIn bipolar depression there is a higher prevalence of atypical features, including hypersomnia and hyperphagia, symptoms that may be observed in bvFTD. In addition, bvFTD and mania share symptoms such as disinhibition, irritability, distractibility, risk taking, impaired social judgment, and excessive involvement in pleasurable activities with potentially harmful consequences (19).Although patients with bvFTD can be inappropriately jocular (20), euphoric mania is accompanied by a qualitatively distinct elevated and expansive mood, with a sense of grandiosity and invulnerability that is uncommon in bvFTD. In addition, in mania irritability is combined with increased energy and decreased need for sleep, a clinical feature not seen in bvFTD.Most importantly, bvFTD involves an inexorable deterioration of cognitive and behavioral functions, while bipolar disorder is usually an episodic syndrome with waxing and waning symptoms. Severe cases of bipolar disorder can evolve toward a chronic state, but cognitive impairment is not as profound or progressive (21).Obsessive-Compulsive Disorder (OCD)Stereotyped and compulsive/ritualistic behaviors due to bvFTD range from simple stereotypies (e.g., rubbing) to more elaborate rituals mimicking compulsions of OCD (e.g., checking, washing) (22). Compulsions can be the initial manifestation of bvFTD (23).Compulsive/ritualistic behaviors can be phenotypically identical in bvFTD and OCD, but there are key distinguishing factors. In OCD, the patients engage in repetitive rituals as a response to obsessions to reduce distress or to "prevent" an adverse outcome. Although the behavior in bvFTD appears seemingly driven by a specific worry, patients usually deny or are unable to describe obsessions (15). It remains unclear whether there are no obsessions, or whether the loss of neuronal function causes an inability to consciously identify obsessions. Importantly, rituals in bvFTD are not typically accompanied by apparent anxiety, which is a core feature of OCD. Most people suffering from OCD have insight that their compulsions are excessive and do not logically prevent dreaded consequences, although some hold on to this possibility. Patients with FTD usually exhibit an almost complete absence of insight.Hoarding can be a prominent feature of bvFTD (24), but it can also manifest as an idiopathic OCD-related disorder. Idiopathic hoarding tends to start in early life and get worse over the years, while in bvFTD it usually follows the onset of cognitive decline. In some cases hoarding may have been present before the onset of bvFTD symptoms and subsequently intensified. Patients with idiopathic hoarding usually accumulate objects with some theoretical value (e.g., paperwork) and endorse weak rationalization about the potential need for future use. In bvFTD, hoarded items can be unsanitary (e.g., rotten food), and hoarding is attributable to impaired decision making rather than anxiety (25).SchizophreniaNegative symptoms of schizophrenia strikingly overlap with the predominantly apathetic variant of bvFTD. Moreover, schizophrenia is associated with mild cognitive deficits in attention, working memory, executive function, declarative memory, and processing speed, which can mimic early deficits of bvFTD (26). The two diseases also share similar social cognitive deficits (27) and limited insight.The clinical distinction is informed by the presence of positive psychotic symptoms, which are relatively rare in FTD (28), and longitudinal history. Schizophrenia usually starts with a prodrome beginning in the late teens to mid-30s, followed by episodic exacerbations and a variable level of residual deficits. Onset of symptoms before age 30–35 is supportive of a primary psychotic disorder; onset of bvFTD before age 30–35 is unusual although possible (29). Most importantly, the course of primary psychotic disorder with periodic exacerbations intertwined with more stable phases is incompatible with bvFTD, which follows a course of progressive neurodegeneration without remission of deficits.Differentiating bvFTD from late-onset schizophrenia (i.e., after age 40) can be more challenging. Late-onset schizophrenia presents with variable combinations of symptoms, including hallucinations (auditory and sometimes other types) and systematized delusions, typically with a lesser degree of negative and cognitive symptoms than is seen in younger patients. Clinical presentations with prominent positive psychotic symptoms unaccompanied by apathy and/or cognitive decline are more likely to be caused by a primary psychotic disorder. One notable exception is the strikingly higher prevalence of psychosis as the initial presentation of bvFTD secondary to C9ORF72 mutations (30, 31) (see the Psychiatric Disorders as a Prodrome of bvFTD section below).CatatoniaCatatonic syndromes and bvFTD share symptoms, including stereotypies, echophenomena, decreased verbal output, and negativism (32). When amenable to cognitive examination, patients with catatonia often show frontal network types of dysfunction such as perseveration and environmental dependency. These syndromes are not mutually exclusive, as catatonia can be a manifestation of bvFTD (33).The diagnosis of catatonia is based on DSM-5 criteria, and it can be supported by a "lorazepam challenge." Rapid improvement of cognitive and behavioral symptoms after the administration of a short-acting benzodiazepine (or ECT) strongly suggests catatonia. Of note, there have been anecdotal reports of persisting cognitive deficits after remission of a catatonic episode (32, 34), which could potentially mimic bvFTD.Neurodevelopmental DisordersDeficits in communication and interpersonal interactions are the core features of autism spectrum disorder (ASD). Similar acquired social cognition deficits are produced by bvFTD, suggesting some degree of shared neuroanatomical circuits (27). Obtaining a collateral developmental history is crucial to differentiate bvFTD from ASD given that symptoms of the latter must be present during early development.It can occasionally be challenging to determine whether distractibility, inattentiveness, and organization deficits are due to long-standing adult attention deficit hyperactivity disorder (ADHD) or to a neurodegenerative process. As with ASD, the key is to elicit a history of similar or more severe ADHD symptoms in childhood. Clinical improvement with psychostimulants is expected to be much more significant in ADHD than in bvFTD (35). While distractibility due to early-stage bvFTD can overlap with symptoms of ADHD, over time the progression of bvFTD will inexorably lead to symptoms that cannot be explained by ADHD, such as loss of empathy or apathy.Personality Traits and Personality DisordersEarly symptoms of bvFTD involve subtle changes in personality and values (36). Relatives often perceive the initial phase as a psychosocial crisis, which can lead to major life changes (e.g., divorce) or legal repercussions (37). In practice, clinicians need to determine whether unusual behaviors reported by relatives should be considered a symptom of an illness or within the realm of normative experience. Indeed, patients with bvFTD often rationalize pathological behaviors as being a normal reaction to events or blame relatives for overreacting.The best strategy, in our experience, is to develop a general sense of premorbid personality by questioning the patient and the family. Reported behaviors can then be analyzed as a function of how much they deviate from the patient's own norms. A particular action might be deemed worrisome in one individual but normal in others. For example, impulsively investing a significant sum of money in a risky venture might be a symptom of disinhibition in someone with a conscientious temperament, but not in a risk-taking entrepreneur. Conversely, patients with bvFTD can exhibit an unusual calmness or ease (38) that can be normal in certain individuals, but pathological in previously dynamic or anxious individuals. If the patient has a psychotherapist, it can be useful to discuss the reported symptoms with the therapist. Longitudinal observations in therapy can provide valuable information that can favor (e.g., inability to engage with therapist) or lead away (e.g., capacity for introspection) from a diagnosis of bvFTD.While it is often difficult to determine whether or not an isolated behavior is pathological, patients with bvFTD will, over time, exhibit multiple unusual behaviors across symptomatic domains (e.g., impulse control, lack of empathy, and so on). Therefore, even if each individual symptom is subtle, bvFTD should be suspected when a patient exhibits multiple types of abnormal behaviors along the lines of bvFTD diagnostic criteria. Of note, with increased public awareness, we have also encountered situations in which families have erroneously interpreted interpersonal conflicts as being symptoms of bvFTD.Diagnosing bvFTD in patients with preexisting personality disorders can be challenging (39, 40). The key diagnostic clue for all personality disorders is their longitudinal nature, with symptoms of maladaptive traits present since early adulthood. Borderline personality disorder and bvFTD can both present with impulsivity, impaired judgment, and anger outbursts. The fear of abandonment, high degree of self-concerns, self-harm, and unstable sense of self differentiate borderline personality disorder from bvFTD. Narcissistic personalities and bvFTD can both have selfishness, disregard for others, and lack of empathy. However, it is not typical for patients with bvFTD to have an excessive sense of self-grandiosity. Patients with bvFTD can exhibit acquired antisocial behaviors, but they usually consist of impulsive actions resulting from disinhibition rather than instrumental aggression (41).Nonprogressive bvFTDA subgroup of patients who meet criteria for possible bvFTD do not show clear deterioration over time (42). These "bvFTD phenocopies" are predominantly men and are less impaired in executive functions, social cognition, and activities of daily living. They do not show supportive features of FTD on neuroimaging (42). Their lifespan is normal, and in many such individuals autopsy has not shown frontotemporal lobar degeneration. While some of these individuals have very slowly progressive forms of bvFTD secondary to C9ORF72 (43), it is generally assumed that many of them do not have bvFTD (42). Some authors have suggested that this phenotype could be a late deterioration of unidentified ASD (Asperger's syndrome) (42, 44). This seems unlikely given the long-standing nature of deficits in ASD. Atypical residual mood disorders, low-grade psychotic disorders, and catatonic syndromes are diagnostic alternatives, but there is much uncertainty as to the nature of this disorder.Psychiatric Disorders as a Prodrome of bvFTDPrimary psychiatric disorders are often diagnosed in the few years preceding a diagnosis of bvFTD (3). While this is in part related to missing the bvFTD diagnosis because of complex symptomatic overlap (45), recent studies (especially related to the C9ORF72 mutation) have highlighted the possibility of bone fide primary psychiatric disorders representing the initial (or prodromal) stage of bvFTD. Among patients with C9ORF72 mutations, a relatively high proportion have late-onset positive psychotic symptoms as the initial presentation (30, 31). Various other neuropsychiatric presentations have been reported, including mania/bipolar disorder (46, 47) and "depressive pseudodementia" (48). However, C9ORF72 mutations are rare (<1%) in cohorts of patients with a clinical diagnosis of schizophrenia (49, 50) or bipolar disorder (46, 51). Based on these findings, patients presenting with late-onset psychiatric disorders should have a careful clinical assessment for bvFTD symptoms and a detailed family history to identify autosomal-dominant disease inheritance patterns.Clinical ApproachIn addition to the psychiatric interview, the clinical assessment should include a family history, a mental status examination, a screening cognitive examination, and a neurological examination. The nature and time course of symptoms should be established, including features that are atypical of primary psychiatric disorders. An atypically late onset age for psychiatric disorders should raise suspicion for a broader differential diagnosis, including neurodegenerative diseases. Behavioral symptoms of bvFTD should be explored with both the patient and at least one informant. The assessment should include screening for cognitive and functional decline.A detailed family history of first- and second-degree relatives for neurological and psychiatric disorders (with particular attention to dementia, ALS, and parkinsonism) is a crucial component of the assessment. A positive family history of mental illness congruent with current psychiatric symptoms supports the diagnosis of a primary psychiatric disorder (52). However, clinicians should be aware that a positive family psychiatric history has been shown to bias toward missing FTD diagnoses (3). Based on the report that primary progressive aphasias are associated with a more frequent family history of developmental language disabilities (53) and our clinical observations, we hypothesize that bvFTD may be associated with an elevated family history of psychiatric disorders. This has not yet been formally investigated, but a recent study showed a higher proportion of psychiatric disorders in relatives of patients with C9ORF72 mutations (54). A family history of early-onset dementia, ALS, late-onset psychiatric syndromes, and unexplained institutionalization in psychiatric hospitals raises suspicion for familial bvFTD. Any late-onset psychiatric presentation in patients with a family history of autosomal-dominant dementia should be assessed for the possibility of a neurodegenerative disorder. In this situation, it is helpful to ask family members to obtain medical records of relatives.Cognitive TestingSpecialized evaluation for neurodegenerative diseases should be pursued aggressively when a patient presents with progressive cognitive impairment in parallel with the new onset of a neuropsychiatric syndrome (55, 56). The first step is to disentangle cognitive weaknesses that can be satisfactorily explained by an acute mental illness from those that cannot. During acute episodes of depression, mania, psychosis, or delirium, attentional disturbances often severely interfere with cognitive performance for a temporary period (57). Persistent and especially progressive executive dysfunction despite improvement in psychiatric symptoms raises the index of suspicion for bvFTD. It is important to keep in mind that severe chronic mental illnesses are associated with multidomain cognitive deficits even between acute exacerbations, but with limited progression over time (26). Deficits due to schizophrenia have been documented prior to the first psychotic episode and can involve multiple cognitive domains, including attention, working memory, verbal learning, verbal memory, and executive functions (performance across testing on average 0.5–2 standard deviations below the mean of age- and education-matched controls) (26, 58). In bipolar disorder, there can be mild and generally stable weaknesses in attention, working memory, lexical fluency, and verbal learning and memory (21, 59).Patients suffering from major depressive episodes and anxiety disorders often express subjective memory concerns. These are usually secondary to primary deficits in attention and working memory, which can have a negative impact on other cognitive domains (e.g., executive functions) and lead to inefficient encoding and retrieval of information (57). Cognitive symptoms are expected to improve in parallel with mood with treatment (60). High antipsychotic dosages and polypharmacy can contribute to cognitive impairment (26, 59); if possible, clinicians should attempt to reduce use of antipsychotics, mood stabilizers, benzodiazepines, and any medication with anticholinergic effects.In the initial stages of bvFTD, the magnitude of cognitive weaknesses can be similar to symptoms observed in primary psychiatric disorders, including major depression (61). The relative specificity of deficits in executive function and language and their progressive nature are characteristics that can help distinguish cognitive impairments in bvFTD from those of severe and persistent mental illnesses (61). Performance on standard screening tests can be within normal limits in early bvFTD (62), and a referral for more in-depth neuropsychological testing is often helpful to identify subtle deficits. Deficits in social cognition are among the earliest impairments in bvFTD and are not captured adequately by standard cognitive tests. Social cognition refers to a cluster of cognitive skills that are required for interpersonal interactions, such as theory of mind, self-knowledge, and perception of others (27). Social cognition batteries, including tests such as identification of interpersonal faux-pas and facial emotion recognition, have been shown to be potentially more sensitive than standard neuropsychological testing for the early diagnosis of bvFTD and to distinguish bvFTD fr