Cortical microstructural changes along the Alzheimer's disease continuum

Victor Montal, Eduard Vilaplana, Daniel Alcolea, Jordi Pegueroles, Ofer Pasternak, Sofia González-Ortiz, Jordi Clarimón, María Carmona-Iragui, Ignacio Illán-Gala, Estrella Morenas-Rodríguez, Roser Ribosa-Nogué, Isabel Sala, María Belén Sánchez-Saudinós, Maite García-Sebastian, Jorge Villanúa, Andrea Izagirre, Ainara Estanga, Mirian Ecay-Torres, Ane Iriondo, Montserrat ClerigueMikel Tainta, Ana Pozueta, Andrea González, Eloy Martínez-Heras, Sara Llufriu, Rafael Blesa, Pascual Sanchez-Juan, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea

Research output: Contribution to journalArticleResearchpeer-review

67 Citations (Scopus)


© 2017 the Alzheimer's Association Introduction: Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD). Methods: We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum. Results: Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages. Discussion: These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.
Original languageEnglish
Pages (from-to)340-351
JournalAlzheimer's and Dementia
Issue number3
Publication statusPublished - 1 Mar 2018


  • Alzheimer's disease continuum
  • Amyloid
  • Biomarkers
  • CSF
  • Cortical microstructure
  • MRI
  • Tau


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