Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer’s disease
Oriol Grau‐Rivera, Irene Navalpotro‐Gómez, Gonzalo Sánchez‐Benavides, Marc Suárez‐Calvet, Marta Milà‐Alomà, Eider M. Arenaza‐Urquijo, Gemma Salvadó, Aleix Sala‐Vila, Mahnaz Shekari, José María Gónzalez‐de‐Echávarri, Carolina Minguillón, Aida Niñerola‐Baizán, Andrés Perissinotti, Maryline Simon, Gwendlyn Kollmorgen, Henrik Zetterberg, Kaj Blennow, Juan Domingo Gispert, José Luís Molinuevo, for the ALFA Study, Annabella Beteta, Raffaele Cacciaglia, Alba Cañas, Carme Deulofeu, Irene Cumplido, Ruth Dominguez, Maria Emilio, Carles Falcón, Sherezade Fuentes, Laura L. Hernandez, Gema Huesa, Jordi Huguet, Karine Fauria, Paula Marne, Tania Menchón, Grégory Operto, Albina Polo, Sandra Pradas, Anna Soteras, Marc Vilanova, Natàlia Vilor‐Tejedor
Abstract
Abstract 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 .