Longitudinal brain structural changes in preclinical Alzheimer's disease

Jordi Pegueroles, Eduard Vilaplana, Victor Montal, Frederic Sampedro, Daniel Alcolea, Maria Carmona-Iragui, Jordi Clarimon, Rafael Blesa, Alberto Lleó, Juan Fortea

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36 Citations (Scopus)


© 2016 the Alzheimer's Association 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 Aβ1–42 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 Aβ1–42 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.
Original languageEnglish
Pages (from-to)499-509
JournalAlzheimer's and Dementia
Issue number5
Publication statusPublished - 1 May 2017


  • Alzheimer's disease
  • Amyloid
  • Biomarkers
  • CSF
  • Longitudinal
  • MRI
  • Tau


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