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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 aim to cha...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890889/ https://www.ncbi.nlm.nih.gov/pubmed/33597012 http://dx.doi.org/10.1186/s13195-021-00781-z |
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author | Grau-Rivera, Oriol Navalpotro-Gomez, 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 |
author_facet | Grau-Rivera, Oriol Navalpotro-Gomez, 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 |
author_sort | Grau-Rivera, Oriol |
collection | PubMed |
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 [(18)F]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. TRIAL REGISTRATION: NCT01835717, NCT02485730, NCT02685969. |
format | Online Article Text |
id | pubmed-7890889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78908892021-02-22 Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer’s disease Grau-Rivera, Oriol Navalpotro-Gomez, 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 Alzheimers Res Ther Research 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 [(18)F]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. TRIAL REGISTRATION: NCT01835717, NCT02485730, NCT02685969. BioMed Central 2021-02-17 /pmc/articles/PMC7890889/ /pubmed/33597012 http://dx.doi.org/10.1186/s13195-021-00781-z Text en © The Author(s) 2021 Open AccessThis 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 made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Grau-Rivera, Oriol Navalpotro-Gomez, 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 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 |
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_short | 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 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890889/ https://www.ncbi.nlm.nih.gov/pubmed/33597012 http://dx.doi.org/10.1186/s13195-021-00781-z |
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