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Alzheimer's Imaging Consortium.

Jorge Garcia Condado1,2,3, Hannah M Klinger1, Colin Birkenbihl1

  • 1Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
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Summary
This summary is machine-generated.

Brain health measured by BrainAge significantly correlates with Alzheimer's biomarkers like amyloid and tau. Worse BrainAge predicts faster cognitive decline, especially with higher biomarker levels, aiding clinical trial selection.

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Area of Science:

  • Neuroimaging and computational neuroscience
  • Biomarkers of neurodegeneration
  • Cognitive aging and Alzheimer's disease

Background:

  • BrainAge models estimate biological brain age from neuroimaging, serving as a brain health indicator.
  • Accelerated brain aging is linked to Alzheimer's disease (AD), driven by amyloid (Aβ) and tau pathology.
  • Investigating BrainAge's moderating role in AD biomarker associations with cognitive decline is crucial.

Purpose of the Study:

  • To assess if BrainAge moderates the relationship between AD biomarkers (Aβ, tau, p-tau217) and longitudinal cognitive decline.
  • To validate findings across two independent cohorts (A4/LEARN and HABS).

Main Methods:

  • Developed BrainAge models using T1-weighted MRI volumetric and cortical thickness data via AgeML.
  • Calculated BrainAge delta (BrainAgedelta) by comparing predicted to chronological age.
  • Utilized linear mixed-effects models to test BrainAgedelta as a moderator of biomarker associations with cognitive performance (PACC), adjusting for covariates.

Main Results:

  • Higher Aβ-PET, Tau-PET, and p-tau217 levels correlated with worse BrainAgedelta.
  • BrainAgedelta directly impacted cognitive trajectories and moderated the association between Aβ/Tau-PET and cognitive decline, indicating faster decline with higher biomarkers and worse BrainAge.
  • Similar moderation was observed for p-tau217 in one cohort.

Conclusions:

  • BrainAgedelta is a robust marker of brain health, significantly associated with AD pathology and cognitive decline.
  • BrainAgedelta moderates the impact of AD biomarkers on cognitive trajectories.
  • Using BrainAgedelta in clinical trials could optimize participant selection and enhance understanding of neurodegeneration.