Social cognition differentiates phenocopy syndrome of behavioural variant frontotemporal dementia from behavioural variant frontotemporal dementia

Background: Patients displaying clinical features of behavioural variant of frontotemporal dementia (bvFTD) but lacking both neuroimaging abnormalities and clinical progression are considered to represent the phenocopy syndrome of bvFTD (phFTD). Extensive clinical overlap between early phase bvFTD and phFTD hampers diagnostic distinction. We aimed to assess the diagnostic value of clinician-rated, self-reported and caregiver-reported symptoms for clinical distinction between phFTD and bvFTD. Methods: There were 33 phFTD and 95 probable bvFTD patients included in the study (total N = 128). Clinician-rated, self-reported tests and caregiver-reported symptoms were compared between phFTD and bvFTD on social cognition, behaviour, mood and activities of daily living (ADL). Scores were compared between groups, followed by multiple logistic regression analysis, adjusted for age and sex. Receiver operating characteristic curves were plotted to assess diagnostic value. Results: Using clinician-rated and self-reported tests, phFTD patients performed better on facial emotion recognition and reported more depressive symptoms. Caregiver-reported behavioural symptoms indicated higher behavioural and ADL impairment in phFTD compared to bvFTD. Facial emotion recognition provided highest diagnostic accuracy for distinction of phFTD from bvFTD (area under the curve (AUC) 0.813 95% CI 0.735–0.892, P < 0.001, sensitivity 81%, specificity 74%) followed by depressive symptoms (AUC 0.769 95% 0.674–0.864, P < 0.001 sensitivity 81%, specificity of 63%). Conclusion: Social cognition tests are most suitable for distinction of phFTD from bvFTD. Caregiver-reported questionnaires and phFTD diagnosis seemed inversely correlated, showing more symptoms in phFTD. Further research is needed on phFTD aetiology and in caregivers taking into account disease burden to assess what explains this discrepancy between clinician-rated and caregiver-based tools

The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the greatest challenges in bvFTD is to capture, measure and predict its disease progression, due to clinical, pathological and genetic heterogeneity. Availability of reliable outcome measures is pivotal for future clinical trials and disease monitoring. Detection of change should be objective, clinically meaningful and easily assessed, preferably associated with a biological process. The purpose of this scoping review is to examine the status of longitudinal studies in bvFTD, evaluate current assessment tools and propose potential progression markers. A systematic literature search (in PubMed and Embase.com) was performed. Literature on disease trajectories and longitudinal validity of frequently-used measures was organized in five domains: global functioning, behavior, (social) cognition, neuroimaging and fluid biomarkers. Evaluating current longitudinal data, we propose an adaptive battery, combining a set of sensitive clinical, neuroimaging and fluid markers, adjusted for genetic and sporadic variants, for adequate detection of disease progression in bvFTD

Late life bipolar disorder evolving into frontotemporal dementia mimic

OBJECTIVES: Although bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series. CASES: From our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3-7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases. CONCLUSION: Symptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical progression. Functional involvement of the frontal-subcortical networks might play a role

Social Cognition Differentiates Behavioral Variant Frontotemporal Dementia From Other Neurodegenerative Diseases and Psychiatric Disorders

Objective: Although deficits in social cognition are established as core features in behavioral variant frontotemporal dementia (bvFTD), it remains unresolved if impaired social cognition distinguishes bvFTD from the broad differential diagnoses in clinical practice. Our aim was to study whether social cognition discriminates bvFTD from other neurodegenerative diseases and psychiatric disorders in patients presenting with late-onset frontal symptoms. Next, we studied the association of social cognition with frontal symptoms and cognitive functioning. Methods: In this longitudinal multicenter study, besides clinical rating scales for frontal symptoms, social cognition was determined by Ekman 60 Faces test and Faux Pas in addition to neuropsychological tests for other cognitive domains in patients with probable and definite bvFTD (N = 22), other neurodegenerative diseases (N = 24), and psychiatric disorders (N = 33). Median symptom duration was 2.8 years, and patients were prospectively followed over 2 years. Results: Total scores from Ekman 60 Faces test were significantly lower in bvFTD than in other neurodegenerative diseases and psychiatric disorders. Ekman 60 Faces test explained 91.2% of the variance of psychiatric disorders and other neurodegenerative diseases versus bvFTD (χ2 = 11.02, df = 1, p = 0.001) and was associated with all other cognitive domains. Faux Pas and the other cognitive domains did not differ between these diagnostic groups. Conclusion: In this clinical sample Ekman 60 Faces test distinguished bvFTD successfully from other neurodegenerative diseases and psychiatric disorders. Although associated with social cognition, other cognitive domains were not discriminative. This study provides arguments to add the Ekman 60 Faces test to the neuropsychological examination in the diagnostic procedure of bvFTD

Gedragsverandering als symptoom

Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disease, the symptoms of which are changes in character, behavioural changes and socio-cognitive changes occurring predominantly at an age between 40 and 70 years. Frontotemporal atrophy is apparent on diagnostic imaging in 70% of patients with bvFTD; a diagnostic dilemma arises if this is not clearly obvious. Validated questionnaires for stereotypical behaviour, depressive symptoms and apathy, and neuropsychological examination can be very helpful in differentiating between bvFTD and psychiatric and other neurological conditions. A brain MRI is always indicated in patients displaying behavioural changes; frontal or temporal atrophy on brain MRI provide sufficient support for the diagnosis 'probable bvFTD'. When in doubt, a supplementary 18F-FDG-PET scan can be performed, but hypometabolism on an 18F-FDG-PET scan can give a false-positive result. If bvFTD is suspected, a multidisciplinary approach, clinical follow-up for 2 years and referral to an FTD centre of excellence are recommended. Conflict of interest and financial support: none declared

Diagnostic Instability Over Time in the Late-Onset Frontal Lobe Syndrome: When Can We Say it's FTD?

Objectives: Distinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We investigated diagnostic instability in a neuropsychiatric cohort up to 8 years after baseline visit and identified which clinical hallmarks contribute to diagnostic instability. Design: Diagnoses of participants of the late-onset frontal lobe (LOF) study were collected from the baseline visit (T0) and the 2-year follow-up visit (T2). Clinical outcomes were retrieved 5–8 years after baseline visit (Tfinal). Endpoint diagnoses were categorized into bvFTD, PPD and other neurological disorders (OND). We calculated the total amount of participants that switched diagnosis between T0-T2 and T2-Tfinal. Clinical records of participants that switched diagnosis were assessed. Results: Of the 137 patients that were included in the study, the final diagnoses at Tfinal were bvFTD 24.1% (n = 33), PPD 39.4% (n = 54), OND 33.6% (n = 46) and unknown 2.9% (n = 4). Between T0 and T2, a total of 29 (21.2%) patients switched diagnosis. Between T2 and Tfinal, 8 (5.8%) patients switched diagnosis. Prolonged follow-up identified few cases with diagnostic instability. Major contributors to diagnostic instability where a nonconverting diagnosis of possible bvFTD and a probable bvFTD diagnosis based on informant-based history and an abnormal FDG-PET scan whilst having a normal MRI. Conclusion: Considering these lessons, a FTD diagnosis remains stable enough to conclude that 2 years is sufficient to say if a patient with late-life behavioral disorder has FTD