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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Daniel D Callow1, Nisha Rani1, Kylie H Alm1

  • 1Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Better hippocampal microstructure, measured by diffusion-weighted imaging, indicates cognitive resilience in Alzheimer's disease (AD). This microstructural integrity helps maintain cognitive function despite tau buildup, unlike hippocampal volume.

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Alzheimer's Disease Research

Background:

  • Cognitive resilience is crucial for maintaining cognitive function in Alzheimer's disease (AD).
  • Hippocampal volume is a known neurodegeneration marker, but hippocampal microstructure via diffusion-weighted imaging (DWI) may offer more sensitive insights.
  • Assessing tissue integrity and cognitive function is vital in AD pathology.

Purpose of the Study:

  • To investigate hippocampal microstructure as a measure of cognitive resilience.
  • To examine if hippocampal microstructure moderates the relationship between tau burden and cognitive performance.
  • To compare DWI metrics with hippocampal volume in relation to tau pathology and cognition.

Main Methods:

  • 192 participants (14 with mild cognitive impairment) from the BIOCARD Study were analyzed.
  • In vivo tau and amyloid burden were measured using positron emission tomography (PET).
  • Hippocampal mean diffusivity (MD) from DWI was used to assess microstructure, with regression analyses controlling for covariates.

Main Results:

  • Lower hippocampal MD (better integrity) significantly attenuated the negative association between tau burden and global cognition.
  • Moderating effects were observed for episodic memory and language, but not executive function or visuospatial abilities.
  • Hippocampal volume did not show a moderating effect on the tau-cognition relationship.

Conclusions:

  • Better hippocampal microstructure is a sensitive biomarker for cognitive resilience in AD.
  • Microstructure may partially mitigate the adverse effects of tau burden on cognition.
  • DWI metrics offer valuable insights into brain mechanisms and potential outcome measures for AD interventions.