Association of cortical microstructure with amyloid-β and tau : impact on cognitive decline, neurodegeneration, and clinical progression in older adults
Rodriguez-Vieitez, Elena (Karolinska Institutet (Estocolm, Suècia))
Montal, Victor (Institut d'Investigació Biomèdica Sant Pau)
Sepulcre, Jorge (Gordon Center for Medical Imaging)
Lois, Cristina (Gordon Center for Medical Imaging)
Hanseeuw, Bernard (Université Catholique de Louvain)
Vilaplana, Eduard (Institut d'Investigació Biomèdica Sant Pau)
Schultz, Aaron P. (Athinoula A. Martinos Center for Biomedical Imaging)
Properzi, Michael J. (Harvard Medical School)
Scott, Matthew R. (Athinoula A. Martinos Center for Biomedical Imaging)
Amariglio, Rebecca (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Papp, Kathryn V. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Marshall, Gad A. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Fortea, Juan (Institut d'Investigació Biomèdica Sant Pau)
Johnson, Keith A. (Gordon Center for Medical Imaging)
Sperling, Reisa A. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Vannini, Patrizia (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	Noninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer's disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression. The study sample comprised n = 196 cognitively normal older adults (mean[SD] 72. 5 [9. 4] years; 114 women [58. 2%]) from the Harvard Aging Brain Study. At baseline, all participants underwent structural MRI, DWI, 11 C-Pittsburgh compound-B-PET, 18 F-flortaucipir-PET imaging, and cognitive assessments. Longitudinal measures of Preclinical Alzheimer Cognitive Composite-5 were available for n = 186 individuals over 3. 72 (1. 96)-year follow-up. Prospective clinical follow-up was available for n = 163 individuals over 3. 2 (1. 7) years. Surface-based image analysis assessed vertex-wise relationships between cMD, global amyloid-β, and entorhinal and inferior-temporal tau. Multivariable regression, mixed effects models and Cox proportional hazards regression assessed longitudinal cognition, brain structural changes and clinical progression. Tau, but not amyloid-β, was positively associated with cMD in AD-vulnerable regions. Correcting for baseline demographics and cognition, increased cMD predicted steeper cognitive decline, which remained significant after correcting for amyloid-β, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-β and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-β, tau, and thickness. Elevated cMD predicted progression to mild cognitive impairment. Cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration and clinical progression, suggesting utility in clinical trials.
Ayudas:	Instituto de Salud Carlos III FI18/00275
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Diagnostic markers ; Psychiatric disorders ; Prognostic markers ; Neuroscience ; Psychology
Publicado en:	Molecular psychiatry, Vol. 26 (september 2021) , p. 7813-7822, ISSN 1476-5578

DOI: 10.1038/s41380-021-01290-z
PMID: 34588623

10 p, 1.6 MB

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