Cortical microstructural changes along the Alzheimer's disease continuum

• Published in: Alzheimer's & dementia Vol. 14; no. 3; pp. 340 - 351
• Main Authors: Montal, Victor, Vilaplana, Eduard, Alcolea, Daniel, Pegueroles, Jordi, Pasternak, Ofer, González-Ortiz, Sofia, Clarimón, Jordi, Carmona-Iragui, María, Illán-Gala, Ignacio, Morenas-Rodríguez, Estrella, Ribosa-Nogué, Roser, Sala, Isabel, Sánchez-Saudinós, María-Belén, García-Sebastian, Maite, Villanúa, Jorge, Izagirre, Andrea, Estanga, Ainara, Ecay-Torres, Mirian, Iriondo, Ane, Clerigue, Montserrat, Tainta, Mikel, Pozueta, Ana, González, Andrea, Martínez-Heras, Eloy, Llufriu, Sara, Blesa, Rafael, Sanchez-Juan, Pascual, Martínez-Lage, Pablo, Lleó, Alberto, Fortea, Juan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018
• Subjects: Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer's disease continuum; Amyloid; Apolipoproteins E - genetics; Biomarkers; Biomarkers - cerebrospinal fluid; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - pathology; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - genetics; Cortical microstructure; CSF; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; MRI; Organ Size; Spinal Puncture; Tau; MRI; CSF; Biomarkers; Tau; Alzheimer's disease continuum; Cortical microstructure; Amyloid
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1016/j.jalz.2017.09.013

Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD). 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. 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. 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.