scholarly journals Young-onset frontotemporal dementia with FUS pathology

2020 ◽  
pp. practneurol-2020-002730
Author(s):  
Matthew Gowell ◽  
Ian Baker ◽  
Olaf Ansorge ◽  
Masud Husain
Keyword(s):  
Frontotemporal Dementia ◽  
Social Withdrawal ◽  
Behavioural Change ◽  
Executive Dysfunction ◽  
Cognitive Testing ◽  
Young Onset ◽  
Fused In Sarcoma ◽  
Severe Impairment ◽  
Characteristic Features ◽  
Relevant Family History

Frontotemporal dementia (FTD) is an uncommon cause of behavioural change in adults under the age of 50. A 44-year-old man presented with progressive neuropsychiatric disturbance characterised by social withdrawal, apathy, loss of empathy, motor stereotypies and hyperorality. Cognitive testing identified severe impairment, including executive dysfunction. MR scan of the brain showed bilateral symmetrical frontal atrophy. There was no relevant family history, and targeted genetic testing for FTD-associated variants in MAPT, GRN and C9orf72 genes proved negative. He became more withdrawn with disinhibited behaviour; his condition progressively worsened and he died 6 years later. The pathological diagnosis was frontotemporal lobar degeneration with fused-in-sarcoma (FUS) pathology, a rare sporadic cause of FTD, accounting for only 5%–10% of cases, its characteristic features including very young onset, motor stereotypies and hyperorality.

scholarly journals A Comparative Study of the Behavioral Profile of the Behavioral Variant of Frontotemporal Dementia and Parkinson’s Disease Dementia

2020 ◽  
pp. 182-194
Author(s):  
Dinesh Saini ◽  
Adreesh Mukherjee ◽  
Arijit Roy ◽  
Atanu Biswas
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Frontotemporal Dementia ◽  
Severe Disease ◽  
Executive Dysfunction ◽  
Behavioral Symptoms ◽  
Parkinson’S Disease Dementia ◽  
Subcortical Dementia ◽  
Behavioral Profile ◽  
Cortical Dementia

<b><i>Background:</i></b> Executive dysfunction is the common thread between pure cortical dementia like the behavioral variant of frontotemporal dementia (bvFTD) and subcortical dementia like Parkinson’s disease dementia (PDD). Although there are clinical and cognitive features to differentiate cortical and subcortical dementia, the behavioral symptoms differentiating these 2 conditions are still not well known. <b><i>Objective:</i></b> To evaluate the behavioral profile of bvFTD and PDD and compare them to find out which behavioral symptoms can differentiate between the two. <b><i>Methods:</i></b> Twenty consecutive patients with bvFTD (&#x3e;1 year after diagnosis) and 20 PDD patients were recruited according to standard diagnostic criteria. Behavioral symptoms were collected from the reliable caregiver by means of a set of questionnaires and then compared between the 2 groups. <b><i>Results:</i></b> bvFTD patients had more severe disease and more behavioral symptoms than PDD. bvFTD patients were different from PDD patients due to their significantly greater: loss of basic emotion (<i>p</i> &#x3c; 0.001, odds ratio [OR] 44.33), loss of awareness of pain (<i>p</i> &#x3c; 0.001, OR 44.33), disinhibition (<i>p</i> &#x3c; 0.001, OR 35.29), utilization phenomenon (<i>p</i> = 0.008, OR 22.78), loss of taste discrimination (<i>p</i> &#x3c; 0.001, OR 17), neglect of hygiene (<i>p</i> = 0.001, OR 13.22), loss of embarrassment (<i>p</i> = 0.003, OR 10.52), wandering (<i>p</i> = 0.004, OR 9.33), pacing (<i>p</i> = 0.014, OR 9), selfishness (<i>p</i> = 0.014, OR 9), increased smoking (<i>p</i> = 0.014, OR 9), increased alcohol consumption (<i>p</i> = 0.031, OR 7.36), social avoidance (<i>p</i> = 0.012, OR 6.93), mutism (<i>p</i> = 0.041, OR 5.67), and failure to recognize objects (<i>p</i> = 0.027, OR 4.33). The bvFTD patients were also significantly less suspicious (<i>p</i> = 0.001, OR 0.0295), less inclined to have a false belief that people were in their home (<i>p</i> = 0.014, OR 0.11) and had fewer visual illusions/hallucinations (<i>p</i> = 0.004, OR 0.107) than PDD patients. <b><i>Conclusion:</i></b> Behavioral symptoms are helpful to distinguish bvFTD from PDD, and thus also cortical dementia with frontal-lobe dysfunction from subcortical dementia.

scholarly journals The Genetics of Monogenic Frontotemporal Dementia

2015 ◽  
Vol 9 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Leonel T. Takada
Keyword(s):  
Frontotemporal Dementia ◽  
Autosomal Dominant ◽  
Positive Family History ◽  
Chromosome 9 ◽  
Complex Phenotype ◽  
Reading Frame ◽  
Protein Tau ◽  
Paget Disease ◽  
Fused In Sarcoma ◽  
Spectrum Disorders

ABSTRACT Around 10-15% of patients diagnosed with frontotemporal dementia (FTD) have a positive family history for FTD with an autosomal dominant pattern of inheritance. Since the identification of mutations in MAPT(microtubuleassociated protein tau gene) in 1998, over 10 other genes have been associated with FTD spectrum disorders, discussed in this review. Along with MAPT, mutations in GRN(progranulin) and C9orf72(chromosome 9 open reading frame 72) are the most commonly identified in FTD cohorts. The association of FTD and motor neuron disease (MND) can be caused by mutations in C9orf72and other genes, such as TARDBP(TAR DNA-binding protein), FUS(fused in sarcoma), UBQLN2(ubiquilin 2). Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP(valosing containing protein) and other recently identified genes.

scholarly journals Executive Dysfunction and Behavioral Symptoms Are Associated with Deficits in Instrumental Activities of Daily Living in Frontotemporal Dementia

2017 ◽  
Vol 43 (1-2) ◽  
pp. 89-99 ◽  
Author(s):  
Negar Moheb ◽  
Mario F. Mendez ◽  
Sarah A. Kremen ◽  
Edmond Teng
Keyword(s):  
Activities Of Daily Living ◽  
Frontotemporal Dementia ◽  
Daily Living ◽  
Primary Progressive Aphasia ◽  
Executive Dysfunction ◽  
Behavioral Symptoms ◽  
Data Set ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Instrumental Activities

Background: Deficits in instrumental activities of daily living (ADLs) may be more prominent in behavioral variant frontotemporal dementia (bvFTD) than in nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or semantic variant primary progressive aphasia (svPPA). It is uncertain whether frontotemporal dementia (FTD) subgroups exhibit different patterns and/or predictors of functional impairment. Methods: We examined data from participants diagnosed with bvFTD (n = 607), svPPA (n = 132), and nfvPPA (n = 155) who were included in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and assessed with the Functional Activities Questionnaire (FAQ). Stepwise multiple linear regression analyses were performed to identify associations between FAQ scores and cognitive/behavioral deficits using the NACC UDS neuropsychological testing battery and the Neuropsychiatric Inventory Questionnaire. Results: FAQ scores were higher in bvFTD than svPPA or nfvPPA. Functional deficits across FTD subtypes differed in severity, but not pattern, and were driven by executive dysfunction and behavioral symptoms. Conclusion: Executive dysfunction and behavioral symptoms underlie instrumental ADL deficits in FTD, which are most prominent in bvFTD.

scholarly journals Dendritic Homeostasis Disruption in a Novel Frontotemporal Dementia Mouse Model Expressing Cytoplasmic Fused in Sarcoma

EBioMedicine ◽  
2017 ◽  
Vol 24 ◽  
pp. 102-115 ◽  
Author(s):  
Gen Shiihashi ◽  
Daisuke Ito ◽  
Itaru Arai ◽  
Yuki Kobayashi ◽  
Kanehiro Hayashi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Frontotemporal Dementia ◽  
Fused In Sarcoma

scholarly journals Investigating Neuroimaging Correlates of Early Frailty in Patients With Behavioral Variant Frontotemporal Dementia: A MRI and FDG-PET Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Martina Amanzio ◽  
Sara Palermo ◽  
Mario Stanziano ◽  
Federico D'Agata ◽  
Antonello Galati ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Frontotemporal Dementia ◽  
Poor Prognosis ◽  
Executive Dysfunction ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Cognitive Dysfunctions ◽  
Frailty Status ◽  
Mood Changes

Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each other within patients. Linear regression of the MPI was performed on those voxels presenting a significant correlation between altered GM volume and metabolism. The neuropsychological assessment reflected the diagnoses and the functional–anatomical alterations documented by neuroimaging analyses. In particular, the majority of patients presented significant executive dysfunction and mood changes in terms of apathy, depression, and anxiety. In the overall MPI score, the patients fell in the lower range (indicating an early frailty status). On imaging, they exhibited a bilateral decrease of GM density and hypometabolism involving the frontal pole, the anterior opercular region, and the anterior cingulate cortex. Greater atrophy than hypometabolism was observed in the bilateral orbitofrontal cortex, the triangular part of the inferior frontal gyrus, and the ventral striatum, whereas the contrary was detected in the bilateral dorsal anterior cingulate cortex and pre-supplementary motor area. MPI scores significantly correlated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.

scholarly journals Altered Cerebrospinal Fluid Exosomal microRNA Levels in Young-Onset Alzheimer’s Disease and Frontotemporal Dementia

2021 ◽  
pp. 1-9
Author(s):  
Yi Jayne Tan ◽  
Benjamin Y.X. Wong ◽  
Ramanathan Vaidyanathan ◽  
Sivaramapanicker Sreejith ◽  
Sook Yoong Chia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Dementia ◽  
Young Onset ◽  
Exosomal Microrna

scholarly journals Expanding the Phenotype of Frontotemporal Lobar Degeneration With FUS-Positive Pathology (FTLD-FUS)

2020 ◽  
Vol 79 (7) ◽  
pp. 809-812 ◽  
Author(s):  
Karina Chornenka ◽  
Veronica Hirsch-Reinshagen ◽  
Mari Perez-Rosendahl ◽  
Howard Feldman ◽  
Freddi Segal-Gidan ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Language Impairment ◽  
Early Onset ◽  
Frontotemporal Lobar Degeneration ◽  
Age Of Onset ◽  
Fused In Sarcoma ◽  
Behavioral Abnormalities ◽  
Early Memory ◽  
High Degree

Abstract Atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions (aFTLD-U) is an uncommon cause of frontotemporal dementia characterized by fused in sarcoma-positive inclusions. It is classified as a subtype of frontotemporal lobar degeneration with FUS pathology. Cases with aFTLD-U pathology typically display an early onset of symptoms and severe psychobehavioral changes in the absence of significant aphasia, cognitive-intellectual dysfunction or motor features. This phenotype is regarded as being sufficiently unusual and consistent as to allow antemortem diagnosis with a high degree of accuracy. In this report, we describe 2 cases with aFTLD-U pathology that broaden the associated phenotype to include later age of onset, milder behavioral abnormalities and early memory and language impairment.

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