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Cortex; a Journal Devoted To the Study... Oct 2018Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study...
Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study addressed areas of contention: the relative roles of the left and right temporal lobe, the contribution of anterior versus posterior temporal cortex and the status of the anterior temporal lobes as amodal hub. Naming and word comprehension was examined in 41 semantic dementia patients, 31 with left-predominant and 10 right-predominant atrophy. In keeping with expectation, naming and comprehension were significantly poorer in left-predominant patients. Structural magnetic resonance image analysis, using a visual rating scale, showed strong inverse correlations between naming scores and severity of both left anterior and posterior temporal lobe atrophy. By contrast, comprehension performance was more strongly correlated with left posterior temporal atrophy. Analysis of naming errors revealed a correlation between anterior temporal atrophy and associative/functional descriptive responses, implying availability of semantic information. By contrast, 'don't know' responses, indicative of loss of semantic knowledge, were linked to left posterior temporal lobe atrophy. Semantic errors, the hallmark of semantic dementia, were linked to right hemisphere atrophy, especially the right posterior temporal lobe. Matched visual-verbal tasks (famous face and name identification, Pyramids and Palm trees pictures and words, animal knowledge from 3-D models and animal names) administered to nine patients elicited variable correspondence between performance on nonverbal and verbal versions of the task. Marked performance dissociations were demonstrated in some patients: poorer understanding of names/words in left-predominant patients and of faces/pictures/models in right-predominant cases. The findings are compatible with the notion of the anterior temporal lobes as areas of convergence, but are less easily accommodated within the framework of amodal conceptual representation. The data, which reconcile some apparent contradictions in the literature, are discussed in the light of the nature and distribution of degenerative change in semantic dementia.
Topics: Aged; Atrophy; Female; Frontotemporal Dementia; Functional Laterality; Humans; Knowledge; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Recognition, Psychology; Semantics; Temporal Lobe
PubMed: 28947063
DOI: 10.1016/j.cortex.2017.08.024 -
Neurotherapeutics : the Journal of the... Apr 2021Frontotemporal dementia encompasses a group of clinical syndromes defined pathologically by degeneration of the frontal and temporal lobes. Historically, these syndromes... (Review)
Review
Frontotemporal dementia encompasses a group of clinical syndromes defined pathologically by degeneration of the frontal and temporal lobes. Historically, these syndromes have been challenging to diagnose, with an average of about three years between the time of symptom onset and the initial evaluation and diagnosis. Research in the field of neuroimaging has revealed numerous biomarkers of the various frontotemporal dementia syndromes, which has provided clinicians with a method of narrowing the differential diagnosis and improving diagnostic accuracy. As such, neuroimaging is considered a core investigative tool in the evaluation of neurodegenerative disorders. Furthermore, patterns of neurodegeneration correlate with the underlying neuropathological substrates of the frontotemporal dementia syndromes, which can aid clinicians in determining the underlying etiology and improve prognostication. This review explores the advancements in neuroimaging and discusses the phenotypic and pathologic features of behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, and nonfluent variant primary progressive aphasia, as seen on structural magnetic resonance imaging and positron emission tomography.
Topics: Biomarkers; Brain; Frontotemporal Dementia; Genetic Variation; Humans; Magnetic Resonance Imaging; Neuroimaging; Positron-Emission Tomography; tau Proteins
PubMed: 34389969
DOI: 10.1007/s13311-021-01101-x -
Annals of the New York Academy of... Mar 2015The concept that frontotemporal dementia (FTD) is a purely cortical dementia has largely been refuted by the recognition of its close association with motor neuron... (Review)
Review
The concept that frontotemporal dementia (FTD) is a purely cortical dementia has largely been refuted by the recognition of its close association with motor neuron disease, and the identification of transactive response DNA-binding protein 43 (TDP-43) as a major pathological substrate underlying both diseases. Genetic findings have transformed this field and revealed connections between disorders that were previous thought clinically unrelated. The discovery that the C9ORF72 locus is responsible for the majority of hereditary FTD, amyotrophic lateral sclerosis (ALS), and FTD-ALS cases and the understanding that repeat-containing RNA plays a crucial role in pathogenesis of both disorders has paved the way for the development of potential biomarkers and therapeutic targets for these devastating diseases. In this review, we summarize the historical aspects leading up to our current understanding of the genetic, clinical, and neuropathological overlap between FTD and ALS, and include brief discussions on chronic traumatic encephalopathy (CTE), given its association with TDP-43 pathology, its associated increased dementia risk, and reports of ALS in CTE patients. In addition, we describe other genetic associations between dementia and neuromuscular disease, such as inclusion body myositis with Paget's disease and FTD.
Topics: Chromosomes, Human, Pair 9; Frontotemporal Dementia; Humans; Neuromuscular Diseases; Open Reading Frames
PubMed: 25557955
DOI: 10.1111/nyas.12638 -
American Journal of Alzheimer's Disease... Nov 2015Frontotemporal dementia (FTD) was one of the lesser known dementias until the recent advancements revealing its genetic and pathological foundation. This common... (Review)
Review
Frontotemporal dementia (FTD) was one of the lesser known dementias until the recent advancements revealing its genetic and pathological foundation. This common neurodegenerative disorder has three clinical subtypes- behavioral, semantic and progressive non fluent aphasia. The behavioral variant mostly exhibits personality changes, while the other two encompass various language deficits. This review discusses the basic pathology, genetics, clinical and histological presentation and the diagnosis of the 3 subtypes. It also deliberates the different therapeutic modalities currently available for frontotemporal dementia and the challenges faced by the caregivers. Lastly it explores the scope of further research into the diagnosis and management of FTD.
Topics: Behavior; Caregivers; Diagnosis, Differential; Frontotemporal Dementia; Humans; Pick Disease of the Brain
PubMed: 23813692
DOI: 10.1177/1533317513494442 -
American Journal of Alzheimer's Disease... Nov 2017Diogenes syndrome refers to the combination of extreme self-neglect and excessive collecting with clutter and squalor, which is often present in patients with dementia.... (Review)
Review
Diogenes syndrome refers to the combination of extreme self-neglect and excessive collecting with clutter and squalor, which is often present in patients with dementia. Diogenes syndrome may be particularly common in behavioral variant frontotemporal dementia (bvFTD), and the investigation of these patients may help clarify the nature of this syndrome. We describe 5 patients with bvFTD who exhibited a decline in self-care accompanied by hoarding behaviors. These patients, and a review of the literature, suggest a combination of frontal lobe disturbances: loss of insight or self-awareness with a failure to clean up or discard, a general compulsive drive, and an innate impulse to take environmental items. This impulse may be part of the environmental dependency syndrome in frontal disease, with specific involvement of a right frontolimbic-striatal system. Further investigation of the similarities and mechanisms of these symptoms in bvFTD could help in understanding Diogenes syndrome and lead to potential treatment options.
Topics: Aged; Frontotemporal Dementia; Humans; Problem Behavior; Self Care; Social Isolation
PubMed: 28660777
DOI: 10.1177/1533317517717012 -
Progress in Molecular Biology and... 2019Frontotemporal dementia is a complex and heterogeneous neurodegenerative disease that encompasses many clinical syndromes, pathological diseases, and genetic mutations.... (Review)
Review
Frontotemporal dementia is a complex and heterogeneous neurodegenerative disease that encompasses many clinical syndromes, pathological diseases, and genetic mutations. Neuroimaging has played a critical role in our understanding of the underlying pathophysiology of frontotemporal dementia and provided biomarkers to aid diagnosis. Early studies defined patterns of neurodegeneration and hypometabolism associated with the clinical, pathological and genetic aspects of frontotemporal dementia, with more recent studies highlighting how the breakdown of structural and functional brain networks define frontotemporal dementia. Molecular positron emission tomography ligands allowing the in vivo imaging of tau proteins have also provided important insights, although more work is needed to understand the biology of the currently available ligands.
Topics: Frontotemporal Dementia; Humans; Imaging, Three-Dimensional; Mutation; Neuroimaging; Speech; tau Proteins
PubMed: 31481163
DOI: 10.1016/bs.pmbts.2019.05.009 -
Practical Neurology Apr 2022A minority (10%-15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological... (Review)
Review
A minority (10%-15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological variants in a single identifiable gene. With the emergence of new therapies targeting specific genetic subtypes of ALS, there is an increasing role for routine genetic testing for all those with a definite diagnosis. However, potential harm to both affected individuals and particularly to asymptomatic relatives can arise from the indiscriminate use of genetic screening, not least because of uncertainties around incomplete penetrance and variants of unknown significance. The most common hereditary cause of ALS, an intronic hexanucleotide repeat expansion in may be associated with frontotemporal dementia independently within the same pedigree. The boundary of what constitutes a possible family history of MND has therefore extended to include dementia and associated psychiatric presentations. Notwithstanding the important role of clinical genetics specialists, all neurologists need a basic understanding of the current place of genetic testing in MND, which holds lessons for other neurological disorders.
Topics: C9orf72 Protein; DNA Repeat Expansion; Frontotemporal Dementia; Genetic Testing; Humans; Proteins
PubMed: 35027459
DOI: 10.1136/practneurol-2021-002989 -
Ugeskrift For Laeger Mar 2017Frontotemporal dementia (FTD) refers to the clinical syndromes caused by various neurodegenerative diseases in the frontal and temporal lobes. Advances in the knowledge... (Review)
Review
Frontotemporal dementia (FTD) refers to the clinical syndromes caused by various neurodegenerative diseases in the frontal and temporal lobes. Advances in the knowledge and understanding of these diseases have resulted in changes in the clinical as well as the genetic and pathological classification. This is a short review of the current classification and understanding of FTD.
Topics: Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Primary Progressive Nonfluent Aphasia
PubMed: 28330541
DOI: No ID Found -
NeuroImage. Clinical 2018Previous literature has revealed that the anterior temporal lobe (ATL) is the semantic hub of left-sided or mixed semantic dementia (SD), whilst the semantic hub of...
INTRODUCTION
Previous literature has revealed that the anterior temporal lobe (ATL) is the semantic hub of left-sided or mixed semantic dementia (SD), whilst the semantic hub of right-sided SD has not been examined.
METHODS
Seventeen patients with right-sided SD, 18 patients with left-sided SD and 20 normal controls (NC) underwent neuropsychological assessments and magnetic resonance imaging scans. We investigated the relationship between the degree of cerebral atrophy in the whole brain and the severity of semantic deficits in left and right-sided SD samples, respectively.
RESULTS
We found the semantic deficits of right-sided SD patients were related to bilateral fusiform gyri and left temporal pole, whilst the left fusiform gyrus correlated with the semantic performance of left-sided SD patients. Moreover, all the findings couldn't be accounted for by total gray matter volume (GMV) or general cognitive degradation of patients.
DISCUSSION
These results provide novel evidence for the current semantic theory, that the important regions for semantic processing include both anterior and posterior temporal lobes.
Topics: Aged; Female; Frontotemporal Dementia; Functional Laterality; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Temporal Lobe
PubMed: 30009130
DOI: 10.1016/j.nicl.2018.05.035 -
Journal of Alzheimer's Disease : JAD 2018The landscape of frontotemporal dementia (FTD) has evolved remarkably in recent years and is barely recognizable from two decades ago. Knowledge of the clinical... (Review)
Review
The landscape of frontotemporal dementia (FTD) has evolved remarkably in recent years and is barely recognizable from two decades ago. Knowledge of the clinical phenomenology, cognition, neuroimaging, genetics, pathology of the different subtypes of FTD, and their relations to other neurodegenerative conditions, has increased rapidly, due in part, to the growing interests into these neurodegenerative brain conditions. This article reviews the major advances in the field of FTD over the past 20 years, focusing primarily on the work of Frontier, the frontotemporal dementia clinical research group, based in Sydney, Australia. Topics covered include clinical presentations (cognition, behavior, neuroimaging), pathology, genetics, and disease progression, as well as interventions and carer directed research. This review demonstrates the improvement in diagnostic accuracy and capacity to provide advice on genetic risks, prognosis, and outcome. The next major challenge will be to capitalize on these research findings to develop effective disease modifying drugs, which are currently lacking.
Topics: Animals; Frontotemporal Dementia; Humans
PubMed: 29504536
DOI: 10.3233/JAD-171087