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

Emma Pineau1, Keying Chen2, Margaret M Koletar2

  • 1University of Toronto, Toronto, ON, Canada.

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

Brain activation pattern variability, measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI), increases with age and cognitive impairment. This variability may serve as a neurophysiological marker for cognitive reserve in Alzheimer's disease (AD).

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Area of Science:

  • Neuroscience
  • Neuroimaging
  • Cognitive Science

Background:

  • The relationship between Alzheimer's disease (AD) pathology and cognitive function, particularly cognitive reserve, remains poorly understood.
  • Neuronal variability in response to stimulation is a known phenomenon but has not been studied on a brain-wide scale.
  • We hypothesize that microscopic neuronal variability leads to macroscopic blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) activation pattern variability, potentially reflecting cognitive reserve.

Purpose of the Study:

  • To investigate brain-wide neuronal activation pattern variability using BOLD fMRI.
  • To explore the relationship between this variability and cognitive reserve in a rat model of AD.
  • To determine if fMRI activation pattern variability is a neurophysiological correlate of cognitive reserve.

Main Methods:

  • Utilized a protracted BOLD fMRI protocol with repetitive somatosensory stimulations in transgenic Fischer 344 rats (TGF344-AD) modeling AD.
  • Analyzed trial-by-trial voxel-level response variability using parametric activation maps and effect-size series.
  • Quantified temporal and spatial variability in activation patterns using Pearson's correlation and categorized animals by age and cognitive status.

Main Results:

  • Brain activation pattern variability was assessed across young, cognitively maintained aged, and cognitively impaired aged rats.
  • The amount of variability in brain activation patterns increased with age and the degree of cognitive impairment.
  • Subjectwise analysis revealed significant group-wise differences in activation pattern variability.

Conclusions:

  • The developed BOLD fMRI assay is sensitive to group-wise differences in activation pattern variability.
  • This variability correlates with cognitive performance in the studied rat model.
  • fMRI activation pattern variability shows potential as a neurophysiological marker for cognitive reserve.