Longitudinal brain structural changes in preclinical Alzheimer's disease

Abstract 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 Aβ 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 Aβ 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.