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Alzheimer's Imaging Consortium.

Ting Qiu1,2,3,4, Zhen-Qi Liu5,6, Jonathan Gallego Rudolf5,7,8

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Summary
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Alzheimer's disease (AD) brain changes begin decades before symptoms, with initial increases in cortical thickness and decreases in mean diffusivity related to amyloid-beta (Aβ) pathology. These nonlinear trajectories precede Aβ positivity onset.

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Area of Science:

  • Neuroimaging
  • Alzheimer's Disease Research
  • Brain Structure Analysis

Background:

  • Alzheimer's disease (AD) involves amyloid-beta (Aβ) and tau pathology, typically linked to grey matter loss.
  • Preclinical AD may paradoxically show increased cortical thickness (CT).
  • Longitudinal neuroimaging is crucial for understanding early AD structural changes.

Purpose of the Study:

  • To investigate associations between Aβ and tau pathology and brain structure (CT, mean diffusivity (MDT), hippocampal volume) over 10 years.
  • To track longitudinal structural changes relative to Aβ positivity timeline.
  • To examine nonlinear trajectories of brain structure changes in preclinical and prodromal AD.

Main Methods:

  • Partial least square analyses (PLS) on Aβ-negative and Aβ-positive groups.
  • Cross-sectional and longitudinal assessment of AD pathology and structural measures.
  • Estimation of time from Aβ positivity onset to track structural changes.

Main Results:

  • Higher Aβ associated with decreased MDT and increased CT in Aβ- group; opposite in Aβ+ group.
  • MDT showed a U-shaped pattern, CT an inverse U-shaped pattern with Aβ pathology.
  • Structural changes emerged years before Aβ positivity, observed in key AD regions.

Conclusions:

  • Brain structural changes in AD begin decades before symptoms, following nonlinear trajectories.
  • Initial CT increases and MDT decreases may relate to Aβ deposition, neuroinflammation, or brain swelling.
  • These findings highlight early, complex structural adaptations in preclinical AD.