The characterization of frontotemporal lobar degeneration (FTLD) is complicated and not widely recognized. Connected language measures (ie, discourse) and functional neuroimaging may advance knowledge specifying early distinctions among frontal dementias. The present study examined the correspondence of discourse measures with (1) clinical diagnosis and (2) single photon emission computed tomography (SPECT) imaging. Nineteen subjects were selected from Alzheimer's Disease Center (ADC) participants if they were diagnosed with early-stage frontotemporal lobar degeneration and also underwent single photon emission computed tomography and discourse evaluation. First, clinical diagnoses given by specialists at an Alzheimer's Disease Center were compared with the discourse-based diagnostic profiles. Secondly, compromised brain regions that were predicted from discourse profiles were compared with SPECT findings. Results revealed a significant correspondence between the ADC diagnosis and the discourse-based diagnoses. Also, the discourse profiles across frontotemporal lobar degeneration subtypes were consistently associated with distinctive patterns of SPECT hypometabolism in the right frontal, left frontal, or left temporal lobes. These findings suggest that discourse methods may be systematized to provide an efficient adjunct measure beyond the traditional word and sentential level measures. Objectifying complex language performance may contribute to early detection and differentiation among frontotemporal lobar degeneration variants because consensus in the literature states that language is a core disturbance of frontotemporal lobar degeneration.
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http://dx.doi.org/10.1097/01.wad.0000189050.41064.03 | DOI Listing |
J Neuropathol Exp Neurol
December 2024
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA).
View Article and Find Full Text PDFBiosensors (Basel)
November 2024
Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43-related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.
Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.
Alzheimers Dement
December 2024
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA.
Introduction: Genetic variation in the lysosomal and transmembrane protein 106B (TMEM106B) modifies risk for several neurodegenerative disorders, especially frontotemporal lobar degeneration (FTLD). The C-terminal (CT) domain of TMEM106B occurs as fibrillar protein deposits in the brains of dementia patients.
Methods: To determine the TMEM CT aggregation propensity and neurodegenerative potential, we generated transgenic Caenorhabditis elegans expressing the human TMEM CT fragment aggregating in FTLD cases.
Glia
December 2024
Department of Neurology and Alzheimer Centre Erasmus MC, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
A subpopulation of astrocytes expressing WD Repeat Domain 49 (WDR49) was recently identified in frontotemporal lobar degeneration (FTLD) with GRN pathogenic variants. This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease (AD). In a postmortem cohort of TDP-43 proteinopathies (12 GRN, 11 C9orf72, 9 sporadic TDP-43), tauopathies (13 MAPT, 8 sporadic tau), 10 AD, and four controls, immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on frontal, temporal, and occipital cortical sections.
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