Longitudinal brain structural changes in preclinical Alzheimer's disease

Introduction: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood. Methods: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates. Results: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF A beta(1-42) levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low A beta(1-42) levels. Discussion: Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.