Association of cortical microstructure with amyloid-beta and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults
Por:
Rodriguez-Vieitez, E, Montal, V, Sepulcre, J, Lois, C, Hanseeuw, B, Vilaplana, E, Schultz, AP, Properzi, MJ, Scott, MR, Amariglio, R, Papp, KV, Marshall, GA, Fortea, J, Johnson, KA, Sperling, RA, Vannini, P
Publicada:
1 dic 2021
Ahead of Print:
1 sep 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-beta 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, C-11-Pittsburgh compound-B-PET, F-18-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-beta, 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-beta, 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-beta, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-beta and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-beta, 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.
Filiaciones:
Rodriguez-Vieitez, E:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Montal, V:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Sepulcre, J:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Gordon Ctr Med Imaging, Boston, MA USA
Lois, C:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Gordon Ctr Med Imaging, Boston, MA USA
Hanseeuw, B:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Gordon Ctr Med Imaging, Boston, MA USA
Catholic Univ Louvain, St Luc Univ Hosp, Brussels, Belgium
Vilaplana, E:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Schultz, AP:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Properzi, MJ:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Scott, MR:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Amariglio, R:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA
Papp, KV:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA
Marshall, GA:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Johnson, KA:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Gordon Ctr Med Imaging, Boston, MA USA
Sperling, RA:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA
Vannini, P:
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA
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