Diverging Progression of Network Disruption and Atrophy in Alzheimer’s Disease and Semantic Dementia

Andreotti, Jennifer; Dierks, Thomas; Wahlund, Lars‐Olof; Grieder, Matthias

doi:10.3233/jad-160571

Cited by 13 publications

(12 citation statements)

References 61 publications

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“…The topological metrics, global efficiency, and path length were useful to discriminate linguistic variants since global efficiency allows a differentiation between nfvPPA and bvFTD while path length differentiates svPPA and controls. Similar results were reported in a recent study; the path length in svPPA was higher in comparison with controls and similar to Alzheimer's disease patients, and it was correlated with the disease progression [ 58 ].…”

Section: Resultssupporting

confidence: 90%

Functional Connectivity Changes in Behavioral, Semantic, and Nonfluent Variants of Frontotemporal Dementia

Reyes

Ortega-Merchan

Rueda

et al. 2018

Behavioural Neurology

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Frontotemporal dementia (FTD) affects behavior, language, and personality. This study aims to explore functional connectivity changes in three FTD variants: behavioral (bvFTD), semantic (svPPA), and nonfluent variant (nfvPPA). Seventy-six patients diagnosed with FTD by international criteria and thirty-two controls were investigated. Functional connectivity from resting functional magnetic resonance imaging (fMRI) was estimated for the whole brain. Two types of analysis were done: network basic statistic and topological measures by graph theory. Several hubs in the limbic system and basal ganglia were compromised in the behavioral variant apart from frontal networks. Nonfluent variants showed a major disconnection with respect to the behavioral variant in operculum and parietal inferior. The global efficiency had lower coefficients in nonfluent variants than behavioral variants and controls. Our results support an extensive disconnection among frontal, limbic, basal ganglia, and parietal hubs.

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Section: Resultssupporting

confidence: 90%

Functional Connectivity Changes in Behavioral, Semantic, and Nonfluent Variants of Frontotemporal Dementia

Reyes

Ortega-Merchan

Rueda

et al. 2018

Behavioural Neurology

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“…Lo anterior también fue soportado por lo hallado en la investigación de Andreotti et al [34], en el cual se recurrió a la modalidad de imágenes de resonancia de difusión para conectividad estructural. En este estudio se encontró que las medidas de LC, EG, FC resultaron afectadas en la variante de demencia semántica respecto de los sujetos sanos y mostraron ser similares a las de pacientes con enfermedad de Alzheimer.…”

Section: Discusiònunclassified

“…Por otro lado, el enfoque estructural que se emplea con la ayuda de la dMRI trata de identificar conexiones "físicas" entre regiones cerebrales a partir de la reconstrucción de los tractos de sustancia blanca. No obstante, para nuestro conocimiento, en la demencia frontotemporal dicha conectividad estructural ha sido explorada en solo un estudio publicado [34], en el cual no se ha efectuado una comparación del comportamiento y/o cambios de las conexiones entre las subvariantes de este trastorno, dado que trabajo con pacientes que padecían demencia semántica y un grupo con Alzheimer. De igual manera, la mayoría de enfoques utilizados en el tratamiento de la información de dMRI para el estudio de las conexiones cerebrales se basa en las métricas de difusión derivadas de esta técnica (fracción anisotrópica, difusividad media), en los que la existencia de una conexión entre regiones, usualmente es definida por valores medios de estas magnitudes.…”

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Análisis de conectividad estructural cerebral en demencia frontotemporal, a partir de imágenes de resonancia de difusión

Santacruz

Reyes

Rueda

2019

RIB

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Resumen-La progresión de los déficits cognitivos en la demencia frontotemporal (DFT) se acompaña de deterioro de la sustancia blanca. El impacto de la pérdida neuronal en la conectividad de la red estructural en la DFT y sus variantes aún no se comprende de manera rigurosa. Se evaluó el potencial del análisis de conectividad estructural cerebral, a partir de imágenes de difusión (dMRI), en la identificación de alteraciones producidas por la DFT y sus variantes, y la relevancia para su diferenciación. Un total de 137 estudios de dMRI divididos en: 20 pacientes con demencia semántica (DS), 20 con afasia progresiva primaria (APP), 52 con variante comportamental (bvDFT) y 45 controles fueron investigados. La conectividad estructural se estimó para todo el cerebro. Se emplearon dos tipos de análisis: medidas topológicas por teoría de grafos y network-based statistic. La organización topológica en las 3 variantes se vio significativamente alterada respecto de los controles, en las medidas de fuerza de conexión, longitud de camino y eficiencia global. La bvDFT se caracterizó por una alteración preferencial interhemisférica centrada en la región frontal del lóbulo izquierdo. En la APP se detectaron pequeñas alteraciones en el giro frontal inferior. Mientras que los pacientes con DS mostraron una mayor extensión de redes alteradas, con desconexiones en el lóbulo temporal de ambos hemisferios. Las alteraciones globales de las redes estructurales sugieren un cambio en la eficiencia de intercambio de información, además de que la localización de dichos cambios se puede asociar con el progreso neuropatológico de la DFT.Palabras clave-Biomarcadores, Conectividad estructural, Demencia frontotemporal, Imagen de difusión por resonancia magnética.Abstract-The progression of cognitive deficits in frontotemporal dementia (FTD) is accompanied by white matter deterioration. However, the impact of neuronal loss on the connectivity of the structural network in the FTD and its variants is not well understood yet. This study aimed to evaluate the potential of structural brain connectivity, in the identification of alterations and changes produced by the FTD and its variants, and the relevance of these measures for its differentiation. A total of 137 studies of dMRI divided as follows: 20 patients with semantic dementia (SD), 20 with progressive primary aphasia (PPA), 52 with behavioral variant (bvFDT) and 45 controls were part of the study. The structural connectivity derived from dMRI was estimated for the whole brain. Two types of analysis were executed: topological measures by graph theory and network-based statistic. Global topological organization in the 3 variants of FTD was significantly altered compared to controls, as seen in measures like connection strength, path length and global efficiency. The bvFTD was characterized by a preferential interhemispheric alteration focused on the frontal region of the left hemisphere. In the PPA a few alterations were detected in the inferior frontal gyrus. While patients with SD showed a great...

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“…Network-based theories suggest that such structural networks are selectively vulnerable in AD (Andreotti et al, 2017). Disrupted functional and structural connectivity has been extensively observed in animal models of Aβ amyloidosis.…”

Section: Introductionmentioning

confidence: 99%

Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis

Al-Amin

Grandjean

Klohs

et al. 2020

Preprint

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Although amyloid beta (Aβ) deposition is one of the major causes of white matter (WM) alterations in Alzheimer's disease (AD), little is known about the underlying basis of WM damage and its association with global structural connectivity and network topology. We aimed to dissect the contributions of WM microstructure to structural connectivity and network properties in the ArcAβ mice model of Aβ amyloidosis.We acquired diffusion-weighted images (DWI) of wild type (WT) and ArcAβ transgenic (TG) mice using a 9.4 T MRI scanner. Fixel-based analysis (FBA) was performed to measure fiber tract-specific properties. We also performed three complementary experiments; to identify the global differences in structural connectivity, to compute network properties and to measure cellular basis of white matter alterations.Transgenic mice displayed disrupted structural connectivity centered to the entorhinal cortex (EC) and a lower fiber density and fiber bundle cross-section. In addition, there was a reduced network efficiency and degree centrality in weighted structural connectivity in the transgenic mice. To further examine the underlying neuronal basis of connectivity and network deficits, we performed histology experiments. We found no alteration in myelination and an increased level of neurofilament light (NFL) in the brain regions with disrupted connectivity in the TG mice. Furthermore, TG mice had a reduced number of perineuronal nets (PNN) in the EC.The observed FDC reductions may indicate a decrease in axonal diameter or axon count which would explain the basis of connectivity deficits and reduced network efficiency in TG mice. The increase in NFL suggests a breakdown of axonal integrity, which would reduce WM fiber health.Considering the pivotal role of the EC in AD, Aβ deposition may primarily increase NFL release, damaging PNN in the entorhinal pathway, resulting in disrupted structural connectivity.

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Diverging Progression of Network Disruption and Atrophy in Alzheimer’s Disease and Semantic Dementia

Cited by 13 publications

References 61 publications

Functional Connectivity Changes in Behavioral, Semantic, and Nonfluent Variants of Frontotemporal Dementia

Functional Connectivity Changes in Behavioral, Semantic, and Nonfluent Variants of Frontotemporal Dementia

Análisis de conectividad estructural cerebral en demencia frontotemporal, a partir de imágenes de resonancia de difusión

Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis

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