Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease

Alzheimer's disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers, such as cerebrospinal fluid (CSF) levels of Aß, p-tau, and t-tau. In parallel, brain anatomy can be characterized through imaging techniques, such as magnetic...

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Autores: Casamitjana Díaz, Adrià|||0000-0002-0539-3638, Petrone, Paula, Molinuevo, Jose Luis, Gispert, Juan Domingo, Vilaplana Besler, Verónica|||0000-0001-6924-9961
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/330701
Acesso em linha:https://hdl.handle.net/2117/330701
https://dx.doi.org/10.3389/fneur.2020.00648
Access Level:acceso abierto
Palavra-chave:Neurology
Diagnostic imaging -- Digital techniques
Alzheimer’s disease
PLS
Pre-clinical AD
Latent model
CSF biomarkers
Brain morphology
Neurologia
Imatgeria per al diagnòstic -- Tècniques digitals
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Neurologia
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Diagnòstic per la imatge
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network_name_str España
repository_id_str
spelling Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's diseaseCasamitjana Díaz, Adrià|||0000-0002-0539-3638Petrone, PaulaMolinuevo, Jose LuisGispert, Juan DomingoVilaplana Besler, Verónica|||0000-0001-6924-9961NeurologyDiagnostic imaging -- Digital techniquesAlzheimer’s diseasePLSPre-clinical ADLatent modelCSF biomarkersBrain morphologyNeurologiaImatgeria per al diagnòstic -- Tècniques digitalsÀrees temàtiques de la UPC::Ciències de la salut::Medicina::NeurologiaÀrees temàtiques de la UPC::Ciències de la salut::Medicina::Diagnòstic per la imatgeAlzheimer's disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers, such as cerebrospinal fluid (CSF) levels of Aß, p-tau, and t-tau. In parallel, brain anatomy can be characterized through imaging techniques, such as magnetic resonance imaging (MRI). In this work we relate both sets of measurements and seek associations between biomarkers and the brain structure that can be indicative of AD progression. The goal is to uncover underlying multivariate effects of AD pathology on regional brain morphological information. For this purpose, we used the projection to latent structures (PLS) method. Using PLS, we found a low dimensional latent space that best describes the covariance between both sets of measurements on the same subjects. Possible confounder effects (age and sex) on brain morphology are included in the model and regressed out using an orthogonal PLS model. We looked for statistically significant correlations between brain morphology and CSF biomarkers that explain part of the volumetric variance at each region-of-interest (ROI). Furthermore, we used a clustering technique to discover a small set of CSF-related patterns describing the AD continuum. We applied this technique to the study of subjects in the whole AD continuum, from the pre-clinical asymptomatic stages all the way through to the symptomatic groups. Subsequent analyses involved splitting the course of the disease into diagnostic categories: cognitively unimpaired subjects (CU), mild cognitively impaired subjects (MCI), and subjects with dementia (AD-dementia), where all symptoms were due to AD.This work has been partially supported by the project MALEGRA TEC2016-75976-R financed by the Spanish Ministerio de Economía y Competitividad and the European Regional Development Fund (ERDF). AC was supported by the Spanish Ministerio de Educación, Cultura y Deporte FPU Research Fellowship. JG holds a Ramón y Cajal fellowship (RYC-2013-13054).Peer Reviewed20202020-07-2820202020-10-23journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/330701https://dx.doi.org/10.3389/fneur.2020.00648reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivs 3.0 Spainhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/3307012026-05-27T15:37:01Z
dc.title.none.fl_str_mv Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
title Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
spellingShingle Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
Casamitjana Díaz, Adrià|||0000-0002-0539-3638
Neurology
Diagnostic imaging -- Digital techniques
Alzheimer’s disease
PLS
Pre-clinical AD
Latent model
CSF biomarkers
Brain morphology
Neurologia
Imatgeria per al diagnòstic -- Tècniques digitals
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Neurologia
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Diagnòstic per la imatge
title_short Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
title_full Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
title_fullStr Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
title_full_unstemmed Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
title_sort Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease
dc.creator.none.fl_str_mv Casamitjana Díaz, Adrià|||0000-0002-0539-3638
Petrone, Paula
Molinuevo, Jose Luis
Gispert, Juan Domingo
Vilaplana Besler, Verónica|||0000-0001-6924-9961
author Casamitjana Díaz, Adrià|||0000-0002-0539-3638
author_facet Casamitjana Díaz, Adrià|||0000-0002-0539-3638
Petrone, Paula
Molinuevo, Jose Luis
Gispert, Juan Domingo
Vilaplana Besler, Verónica|||0000-0001-6924-9961
author_role author
author2 Petrone, Paula
Molinuevo, Jose Luis
Gispert, Juan Domingo
Vilaplana Besler, Verónica|||0000-0001-6924-9961
author2_role author
author
author
author
dc.subject.none.fl_str_mv Neurology
Diagnostic imaging -- Digital techniques
Alzheimer’s disease
PLS
Pre-clinical AD
Latent model
CSF biomarkers
Brain morphology
Neurologia
Imatgeria per al diagnòstic -- Tècniques digitals
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Neurologia
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Diagnòstic per la imatge
topic Neurology
Diagnostic imaging -- Digital techniques
Alzheimer’s disease
PLS
Pre-clinical AD
Latent model
CSF biomarkers
Brain morphology
Neurologia
Imatgeria per al diagnòstic -- Tècniques digitals
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Neurologia
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Diagnòstic per la imatge
description Alzheimer's disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers, such as cerebrospinal fluid (CSF) levels of Aß, p-tau, and t-tau. In parallel, brain anatomy can be characterized through imaging techniques, such as magnetic resonance imaging (MRI). In this work we relate both sets of measurements and seek associations between biomarkers and the brain structure that can be indicative of AD progression. The goal is to uncover underlying multivariate effects of AD pathology on regional brain morphological information. For this purpose, we used the projection to latent structures (PLS) method. Using PLS, we found a low dimensional latent space that best describes the covariance between both sets of measurements on the same subjects. Possible confounder effects (age and sex) on brain morphology are included in the model and regressed out using an orthogonal PLS model. We looked for statistically significant correlations between brain morphology and CSF biomarkers that explain part of the volumetric variance at each region-of-interest (ROI). Furthermore, we used a clustering technique to discover a small set of CSF-related patterns describing the AD continuum. We applied this technique to the study of subjects in the whole AD continuum, from the pre-clinical asymptomatic stages all the way through to the symptomatic groups. Subsequent analyses involved splitting the course of the disease into diagnostic categories: cognitively unimpaired subjects (CU), mild cognitively impaired subjects (MCI), and subjects with dementia (AD-dementia), where all symptoms were due to AD.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-07-28
2020
2020-10-23
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/330701
https://dx.doi.org/10.3389/fneur.2020.00648
url https://hdl.handle.net/2117/330701
https://dx.doi.org/10.3389/fneur.2020.00648
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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