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Related Experiment Video

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

Jiaqi Wen1,2, Chenyang Li3, Zhe Sun3

  • 1New York University Grossman School of Medicine, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary

Aging affects the hippocampus, with arterial transit time (ATT) more vulnerable than cerebral blood flow (CBF). Sex differences emerge, with female brains showing greater susceptibility to age-related changes in the hippocampus and connected regions.

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Area of Science:

  • Neuroscience
  • Aging Research
  • Neuroimaging

Background:

  • The hippocampus, crucial for cognition, undergoes age-related structural and vascular changes.
  • Understanding the interplay between hippocampus structure, vascular function, and connected brain regions is vital, especially considering sex-specific aging patterns.
  • Hormonal changes in older women may increase vulnerability to aging effects.

Purpose of the Study:

  • To investigate the relationship between structural and vascular alterations in hippocampus subfields and connected prefrontal and entorhinal cortex during healthy aging.
  • To explore how these age-related changes influence cognitive function.
  • To identify sex-specific patterns in these neurobiological changes.

Main Methods:

  • Utilized T1-MPRAGE and pseudo-continuous arterial spin labeling (pCASL) data from 650 subjects in the HCP-Aging dataset.
  • Segmented prefrontal cortex, entorhinal cortex, and hippocampus subfields (subiculum, CA1-4, dentate gyrus) using FreeSurfer and Hippfold.
  • Processed pCASL data to obtain cerebral blood flow (CBF) and arterial transit time (ATT) in hippocampus subfields; cognitive function assessed using composite scores.

Main Results:

  • All hippocampal subfields showed age-related atrophy; ATT was more sensitive to aging and correlated more strongly with atrophy than CBF.
  • The CA1 subfield exhibited the lowest perfusion and strongest association with atrophy. Female hippocampal subfields were more susceptible to aging and atrophy than males.
  • In males, subiculum CBF may compensate for atrophy. Prefrontal cortex showed greater perfusion decline than entorhinal cortex. CA1 atrophy impacts cognition via delayed ATT in the prefrontal cortex in females.

Conclusions:

  • Established relationships between structure and vascular function in the hippocampus and connected cortical regions, highlighting age-related, sex-specific, and subfield-specific changes.
  • Findings offer insights into mechanisms underlying age-related neurodegenerative diseases like Alzheimer's.
  • The study underscores the importance of considering subfield and sex differences in aging brain research.