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Vogt, Nicholas M.; Hunt, Jack F. V.; Adluru, Nagesh; Ma, Yue; Van Hulle, Carol A.; III, Douglas C. Dean; Kecskemeti, Steven R.; Chin, Nathaniel A.; Carlsson, Cynthia M.; Asthana, Sanjay; Johnson, Sterling C.; Kollmorgen, Gwendlyn; Batrla, Richard; Wild, Norbert; Buck, Katharina; Zetterberg, Henrik; Alexander, Andrew L.; Blennow, Kaj; Bendlin, Barbara B.

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults

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  • Media type: E-Article
  • Title: Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults
  • Contributor: Vogt, Nicholas M.; Hunt, Jack F. V.; Adluru, Nagesh; Ma, Yue; Van Hulle, Carol A.; III, Douglas C. Dean; Kecskemeti, Steven R.; Chin, Nathaniel A.; Carlsson, Cynthia M.; Asthana, Sanjay; Johnson, Sterling C.; Kollmorgen, Gwendlyn; Batrla, Richard; Wild, Norbert; Buck, Katharina; Zetterberg, Henrik; Alexander, Andrew L.; Blennow, Kaj; Bendlin, Barbara B.
  • imprint: Wiley, 2022
  • Published in: Alzheimer's & Dementia
  • Language: English
  • DOI: 10.1002/alz.12364
  • ISSN: 1552-5260; 1552-5279
  • Keywords: Psychiatry and Mental health ; Cellular and Molecular Neuroscience ; Geriatrics and Gerontology ; Neurology (clinical) ; Developmental Neuroscience ; Health Policy ; Epidemiology
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  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Neurite orientation dispersion and density imaging (NODDI), a multi‐compartment diffusion‐weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using neuroimaging (NODDI and T1‐weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)<jats:sub>42</jats:sub>/Aβ<jats:sub>40</jats:sub> and phosphorylated tau (p‐tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We observed a significant CSF Aβ<jats:sub>42</jats:sub>/Aβ<jats:sub>40</jats:sub> × p‐tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p‐tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p‐tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.</jats:p></jats:sec>