Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer’s disease

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 [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