Cytoarchitectonic gradients of laminar degeneration in behavioural variant frontotemporal dementia DOI
Daniel T. Ohm, Sharon X. Xie,

Noah Capp

et al.

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Abstract Behavioural variant frontotemporal dementia (bvFTD) is a clinical syndrome caused primarily by either tau (bvFTD-tau) or transactive response DNA-binding protein of 43 kDa (TDP-43) (bvFTD-TDP) proteinopathies. We previously found that lower cortical layers and dorsolateral regions accumulate greater than TDP-43 pathology; however, the patterns laminar neurodegeneration across diverse cytoarchitecture in bvFTD are understudied. hypothesized bvFTD-tau bvFTD-TDP have distinct distributions pyramidal along gradients, topological order cytoarchitectonic subregions based on increasing density differentiation. Here, we tested this hypothesis frontal gradient consisting five types (i.e. periallocortex, agranular mesocortex, dysgranular eulaminate-I isocortex eulaminate-II isocortex) spanning anterior cingulate, paracingulate, orbitofrontal mid-frontal gyri (n = 27), 47) healthy controls 32). immunostained all tissue for total neurons (NeuN; neuronal-nuclear protein) (SMI32; non-phosphorylated neurofilament) digitally quantified NeuN-immunoreactivity (ir) SMI32-ir supragranular II–III, infragranular V–VI I–VI each type. used linear mixed-effects models adjusted demographic biological variables to compare between groups examine relationships with gradient, long-range pathways symptoms. regional expected controls, validating our measures within framework. The loss was relatively uniform bvFTD-TDP, whereas decreased progressively included versus (P 0.039). Using ratio model known connectivity mesocortex isocortex, larger 0.019), suggesting select long-projecting might contribute isocortical-predominant degeneration bvFTD-tau. In highest NeuN-ir, 0.047), occur earlier Lastly, reduced related behavioural severity frontal-mediated letter fluency, not temporal-mediated confrontation naming, demonstrating relevance specificity bvFTD-related Our data suggest neurofilament-rich clinically relevant feature worsens selectively bvFTD-tau, bvFTD-TDP. Therefore, tau-mediated preferentially involve pyramidal-rich connect more distant types. Moreover, hierarchical arrangement gradients be an important neuroanatomical framework identifying which cells involved differentially

Language: Английский

Automated Speech Analysis to Differentiate Frontal and Right Anterior Temporal Lobe Atrophy in Frontotemporal Dementia DOI
Jet M. J. Vonk,

Brittany Morin,

Janhavi Pillai

et al.

Neurology, Journal Year: 2025, Volume and Issue: 104(9)

Published: April 10, 2025

Frontotemporal dementia (FTD) includes behavioral-variant FTD (bvFTD) with predominant frontal atrophy and semantic (sbvFTD) right anterior temporal lobe (rATL) atrophy. These variants present diagnostic challenges because of overlapping symptoms neuroanatomy. Accurate differentiation is crucial for clinical trial inclusion targeting TDP-43 proteinopathies. This study investigated whether automated speech analysis can distinguish between FTD-related rATL atrophy, potentially offering a noninvasive tool. cross-sectional used data from the University California, San Francisco Memory Aging Center. Using stepwise logistic regression receiver-operating characteristic curve analysis, we analyzed 16 linguistic acoustic features that were extracted automatically audio-recorded picture description tasks. Voxel-based morphometry was to investigate brain-behavior relationships. We evaluated 62 participants: 24 22 healthy controls (mean age 68.3 years, SD = 9.2; 53.2% female). Logistic identified 3 (content units, lexical frequency, familiarity) differentiating overall group (area under [AUC] 0.973), adjusted age. Within group, 5 (adpositions/total words ratio, arousal, syllable pause duration, restarts, containing "thing") differentiated (AUC 0.943). Neuroimaging analyses showed (lexical content "thing" words) linked bilateral inferior structures, (syllable adpositions/total ratio) gyri, socioemotional (arousal) areas known mediate social cognition including insula structures. As composite score, this set uniquely associated Automated demonstrated high accuracy in subtypes provided insights into neural basis language impairments. could enhance early diagnosis monitoring FTD, scalable, alternative traditional methods, particularly resource-limited settings. Future research should focus on further validation other neuroimaging or fluid biomarkers longitudinal cognitive data, as well external larger more diverse populations.

Language: Английский

Citations

0
Cytoarchitectonic gradients of laminar degeneration in behavioral variant frontotemporal dementia DOI Open Access
Daniel T. Ohm, Sharon X. Xie,

Noah Capp

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 9, 2024

ABSTRACT Behavioral variant frontotemporal dementia (bvFTD) is a clinical syndrome primarily caused by either tau (bvFTD-tau) or TDP-43 (bvFTD-TDP) proteinopathies. We previously found lower cortical layers and dorsolateral regions accumulate greater than pathology; however, patterns of laminar neurodegeneration across diverse cytoarchitecture in bvFTD understudied. hypothesized that bvFTD-tau bvFTD-TDP have distinct distributions pyramidal along gradients, topologic order cytoarchitectonic subregions based on increasing density differentiation. Here, we tested this hypothesis frontal gradient consisting five types (i.e., periallocortex, agranular mesocortex, dysgranular eulaminate-I isocortex, eulaminate-II isocortex) spanning anterior cingulate, paracingulate, orbitofrontal, mid-frontal gyri (n=27), (n=47), healthy controls (HC; n=32). immunostained all tissue for total neurons (NeuN; neuronal-nuclear protein) (SMI32; non-phosphorylated neurofilament) digitally quantified NeuN-immunoreactivity (ir) SMI32-ir supragranular II-III, infragranular V-VI, I-VI each type. used linear mixed-effects models adjusted demographic biologic variables to compare between groups examine relationships with the gradient, long-range pathways, symptoms. regional expected HC, validating our measures within framework. While loss was not related bvFTD-TDP, progressively decreased included isocortex vs ( p =0.039). In structural model connectivity mesocortex larger ratio mesocortex-to-isocortex =0.019), suggesting select long-projecting pathways may contribute isocortical-predominant degeneration bvFTD-tau. highest NeuN-ir, =0.047), occur earlier Lastly, reduced behavioral severity frontal-mediated letter fluency, temporal-mediated confrontation naming, demonstrating relevance specificity bvFTD-related Our data suggest neurofilament-rich clinically relevant feature selectively worsens bvFTD-tau, bvFTD-TDP. Therefore, tau-mediated preferentially involve pyramidal-rich connect more distant types. Moreover, hierarchical arrangement gradients be an important neuroanatomical framework identifying which cells are differentially involved

Language: Английский

Citations

1
Digital language markers distinguish frontal from right anterior temporal lobe atrophy in frontotemporal dementia DOI Creative Commons
Jet M. J. Vonk,

Brittany Morin,

Janhavi Pillai

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Within frontotemporal dementia (FTD), the behavioral variant (bvFTD) characterized by frontal atrophy, and semantic (sbvFTD) right anterior temporal lobe (rATL) present diagnostic challenges due to overlapping symptoms neuroanatomy. Accurate differentiation is crucial for clinical trial inclusion targeting TDP-43 proteinopathies. This study investigated whether automated speech analysis can distinguish between FTD-related rATL potentially offering a non-invasive tool.

Language: Английский

Citations

1
Clinical Recognition of Frontotemporal Dementia with Right Anterior Temporal Predominance; Consensus Recommendations of the International Working Group DOI Creative Commons
Hülya Ulugut, Kyan Younes, Maxime Montembeault

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract Accurate diagnosis of frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance remains challenging due to lack clinical characterization, and standardized terminology. The recent research the International Working Group (IWG) identified common symptoms but also unveiled broad terminologies lacking precision operationalization, risk misdiagnoses, inappropriate referrals poor management. Based on published evidence (91267 articles screened) expert opinion (105 FTD specialists across 52 centers), IWG delineates three primary domains impairment causing behavioral, memory language problems: (i) multimodal knowledge non-verbal information including people, living beings, landmarks, flavors/odors, sounds, bodily sensations, emotions social cues; (ii) socioemotional behavior encompassing emotion expression, response motivation; (iii) prioritization for focus specific interests, hedonic valuation personal preferences. This study establishes a consensus profile, phenotypic nomenclature, future directions enhance diagnostic therapeutic interventions.

Language: Английский

Citations

1
Cytoarchitectonic gradients of laminar degeneration in behavioural variant frontotemporal dementia DOI
Daniel T. Ohm, Sharon X. Xie,

Noah Capp

et al.

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Abstract Behavioural variant frontotemporal dementia (bvFTD) is a clinical syndrome caused primarily by either tau (bvFTD-tau) or transactive response DNA-binding protein of 43 kDa (TDP-43) (bvFTD-TDP) proteinopathies. We previously found that lower cortical layers and dorsolateral regions accumulate greater than TDP-43 pathology; however, the patterns laminar neurodegeneration across diverse cytoarchitecture in bvFTD are understudied. hypothesized bvFTD-tau bvFTD-TDP have distinct distributions pyramidal along gradients, topological order cytoarchitectonic subregions based on increasing density differentiation. Here, we tested this hypothesis frontal gradient consisting five types (i.e. periallocortex, agranular mesocortex, dysgranular eulaminate-I isocortex eulaminate-II isocortex) spanning anterior cingulate, paracingulate, orbitofrontal mid-frontal gyri (n = 27), 47) healthy controls 32). immunostained all tissue for total neurons (NeuN; neuronal-nuclear protein) (SMI32; non-phosphorylated neurofilament) digitally quantified NeuN-immunoreactivity (ir) SMI32-ir supragranular II–III, infragranular V–VI I–VI each type. used linear mixed-effects models adjusted demographic biological variables to compare between groups examine relationships with gradient, long-range pathways symptoms. regional expected controls, validating our measures within framework. The loss was relatively uniform bvFTD-TDP, whereas decreased progressively included versus (P 0.039). Using ratio model known connectivity mesocortex isocortex, larger 0.019), suggesting select long-projecting might contribute isocortical-predominant degeneration bvFTD-tau. In highest NeuN-ir, 0.047), occur earlier Lastly, reduced related behavioural severity frontal-mediated letter fluency, not temporal-mediated confrontation naming, demonstrating relevance specificity bvFTD-related Our data suggest neurofilament-rich clinically relevant feature worsens selectively bvFTD-tau, bvFTD-TDP. Therefore, tau-mediated preferentially involve pyramidal-rich connect more distant types. Moreover, hierarchical arrangement gradients be an important neuroanatomical framework identifying which cells involved differentially

Language: Английский

Citations

0