Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer’s disease
Authors: 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 ,   for the ALFA Study, Beteta Annabella , Cacciaglia Raffaele , Cañas Alba , Deulofeu Carme , Cumplido Irene , Dominguez Ruth , Emilio Maria , Falcon Carles , Fuentes Sherezade , Hernandez Laura , Huesa Gema , Huguet Jordi , Fauria Karine , Marne Paula , Menchón Tania , Operto Grégory , Polo Albina , Pradas Sandra , Soteras Anna , Vilanova Marc , Vilor-Tejedor Natàlia 
Published: February 2021

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 = − 0.147p = 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.