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Drug Development.

Mohammed U Al-Youzbaki1, Salonee V Patel1, Ashley L Schormans1

  • 1Western University, London, ON, Canada.

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|December 26, 2025
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Summary
This summary is machine-generated.

Decision-making modeling revealed early Alzheimer's disease (AD) changes in a preclinical rat model. This approach identified genotype- and sex-specific cognitive alterations not seen in standard tests, aiding biomarker discovery.

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Area of Science:

  • Neuroscience
  • Computational Psychiatry
  • Animal Models of Disease

Background:

  • Clinical studies demonstrate the utility of mathematical decision-making models for identifying behavioral biomarkers in dementia.
  • Preclinical research is essential for understanding early-stage neurodegenerative diseases like Alzheimer's disease (AD).

Purpose of the Study:

  • To integrate decision-making modeling into behavioral analysis of a prodromal rat model of AD.
  • To uncover genotype- and sex-specific behavioral effects not apparent through standard performance assessments.

Main Methods:

  • Male and female wildtype and transgenic Fischer 344 rats (TgAPP) performed a visual discrimination task.
  • Reaction times were analyzed using an ExGauss function to assess variability.
  • Decision-making processes were modeled using a drift diffusion model (DDM) to quantify evidence accumulation, decision thresholds, and non-decision time.

Main Results:

  • Transgenic APP (TgAPP) rats exhibited lower accuracy and slower reaction times compared to wildtypes, with females showing increased timing variability.
  • DDM analysis revealed slower evidence accumulation in both male and female TgAPP rats.
  • Female TgAPP rats displayed higher decision thresholds and increased non-decision times, indicating enhanced response caution and altered processing.

Conclusions:

  • Drift diffusion modeling effectively identifies cognitive function changes in a prodromal AD rat model, surpassing standard metrics.
  • Combining computational modeling with other biomarkers can improve understanding of early AD and preclinical research translation.