Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease
Background: Recognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We a...
| Autores: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/47146 |
| Acceso en línea: | http://hdl.handle.net/10230/47146 http://dx.doi.org/10.1186/s13195-021-00781-z |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer’s disease Biomarkers Cognitively unimpaired Preclinical Risk factors Weight loss |
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Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| title |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| spellingShingle |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease Grau, Oriol (Grau Rivera) Alzheimer’s disease Biomarkers Cognitively unimpaired Preclinical Risk factors Weight loss |
| title_short |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| title_full |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| title_fullStr |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| title_full_unstemmed |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| title_sort |
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease |
| dc.creator.none.fl_str_mv |
Grau, Oriol (Grau Rivera) Navalpotro-Gómez, Irene Sánchez Benavides, Gonzalo Suárez-Calvet, Marc Milà Alomà, Marta Arenaza Urquijo, Eider M. Salvadó, Gemma Sala Vila, Aleix Shekari, Mahnaz González de Echávarri, José Maria Minguillón, Carolina Niñerola-Baizán, Aida Perissinotti, Andrés Simon, Maryline Kollmorgen, Gwendlyn Zetterberg, Henrik Blennow, Kaj Gispert, Juan Domingo Molinuevo, José Luis ALFA Study |
| author |
Grau, Oriol (Grau Rivera) |
| author_facet |
Grau, Oriol (Grau Rivera) Navalpotro-Gómez, Irene Sánchez Benavides, Gonzalo Suárez-Calvet, Marc Milà Alomà, Marta Arenaza Urquijo, Eider M. Salvadó, Gemma Sala Vila, Aleix Shekari, Mahnaz González de Echávarri, José Maria Minguillón, Carolina Niñerola-Baizán, Aida Perissinotti, Andrés Simon, Maryline Kollmorgen, Gwendlyn Zetterberg, Henrik Blennow, Kaj Gispert, Juan Domingo Molinuevo, José Luis ALFA Study |
| author_role |
author |
| author2 |
Navalpotro-Gómez, Irene Sánchez Benavides, Gonzalo Suárez-Calvet, Marc Milà Alomà, Marta Arenaza Urquijo, Eider M. Salvadó, Gemma Sala Vila, Aleix Shekari, Mahnaz González de Echávarri, José Maria Minguillón, Carolina Niñerola-Baizán, Aida Perissinotti, Andrés Simon, Maryline Kollmorgen, Gwendlyn Zetterberg, Henrik Blennow, Kaj Gispert, Juan Domingo Molinuevo, José Luis ALFA Study |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Alzheimer’s disease Biomarkers Cognitively unimpaired Preclinical Risk factors Weight loss |
| topic |
Alzheimer’s disease Biomarkers Cognitively unimpaired Preclinical Risk factors Weight loss |
| description |
Background: Recognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults. Methods: This prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n = 2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [18F]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1 years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change. Results: Weight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00-1.61, p = 0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19-1.89, p = 0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25-2.20, p = 0.001) and was greater among participants with an A+T+ profile (p < 0.01) at follow-up. Weight change was positively associated with CSF Aβ42/40 ratio (β = 0.099, p = 0.032) and negatively associated with CSF p-tau (β = - 0.141, p = 0.005), t-tau (β = - 0.147 p = 0.004) and neurogranin levels (β = - 0.158, p = 0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only. Conclusions: Weight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-β accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2021 2021 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/47146 http://dx.doi.org/10.1186/s13195-021-00781-z |
| url |
http://hdl.handle.net/10230/47146 http://dx.doi.org/10.1186/s13195-021-00781-z |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.relation.none.fl_str_mv |
Alzheimers Res Ther. 2021;13(1):46 info:eu-repo/grantAgreement/EC/H2020/752310 |
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http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf |
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BioMed Central |
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BioMed Central |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's diseaseGrau, Oriol (Grau Rivera)Navalpotro-Gómez, IreneSánchez Benavides, GonzaloSuárez-Calvet, MarcMilà Alomà, MartaArenaza Urquijo, Eider M.Salvadó, GemmaSala Vila, AleixShekari, MahnazGonzález de Echávarri, José MariaMinguillón, CarolinaNiñerola-Baizán, AidaPerissinotti, AndrésSimon, MarylineKollmorgen, GwendlynZetterberg, HenrikBlennow, KajGispert, Juan DomingoMolinuevo, José LuisALFA StudyAlzheimer’s diseaseBiomarkersCognitively unimpairedPreclinicalRisk factorsWeight lossBackground: Recognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults. Methods: This prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n = 2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [18F]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1 years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change. Results: Weight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00-1.61, p = 0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19-1.89, p = 0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25-2.20, p = 0.001) and was greater among participants with an A+T+ profile (p < 0.01) at follow-up. Weight change was positively associated with CSF Aβ42/40 ratio (β = 0.099, p = 0.032) and negatively associated with CSF p-tau (β = - 0.141, p = 0.005), t-tau (β = - 0.147 p = 0.004) and neurogranin levels (β = - 0.158, p = 0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only. Conclusions: Weight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-β accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment.Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. OG-R is supported by the Spanish Ministry of Science, Innovation and Universities (FJCI-2017-33437) and receives funding from the Alzheimer’s Association Research Fellowship Program (2019-AARF-644568). MS-C received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310 and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). EMA-U is supported by the Spanish Ministry of Science, Innovation and Universities - Spanish State Research Agency (RYC2018-026053-I). ASV is the recipient of an Instituto de Salud Carlos III Miguel Servet II fellowship (CP II 17/00029). JDG holds a “Ramón y Cajal” fellowship (RYC-2013-13054). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. KB is supported by the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236).BioMed Central202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/47146http://dx.doi.org/10.1186/s13195-021-00781-zreponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésAlzheimers Res Ther. 2021;13(1):46info:eu-repo/grantAgreement/EC/H2020/752310© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data mahttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/471462026-05-29T05:05:01Z |
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15,812455 |