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Clinical Manifestations.

Gurshaan Sidhu1, Dylan X Guan2, Maryam Ghahremani2

  • 1University of Calgary, Calgary, AB, Canada.

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

Cognitive reserve (CR) buffers against neuropsychiatric symptoms (NPS) linked to hippocampal atrophy in older adults. Higher CR levels reduce the impact of brain changes on behavior, offering protection beyond cognitive function.

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Area of Science:

  • Neuroscience
  • Gerontology
  • Psychiatry

Background:

  • Cognitive reserve (CR) mitigates cognitive decline in neurodegenerative diseases like Alzheimer's (AD).
  • The relationship between CR and neuropsychiatric symptoms (NPS) in neurodegenerative conditions is less understood.
  • AD-related brain atrophy, particularly in the hippocampus and entorhinal cortex, is linked to NPS.

Purpose of the Study:

  • To investigate the moderating effect of CR on the association between hippocampal and entorhinal cortex atrophy and NPS in older adults.
  • To determine if CR influences the manifestation of NPS in the presence of neurodegenerative brain changes.

Main Methods:

  • Utilized data from 455 participants in the COMPASS-ND study with varying cognitive statuses.
  • Calculated a composite CR score (CRS) from education, occupation, and personal activities.
  • Employed logistic regression to model the relationship between hippocampal/entorhinal atrophy and NPS, testing for CRS interaction effects.

Main Results:

  • Higher CRS correlated with better cognitive scores (MoCA) and lower likelihood of NPS.
  • Significant evidence indicated that hippocampal atrophy was less associated with NPS in individuals with higher CR.
  • A similar trend was observed for entorhinal atrophy, though not statistically significant.

Conclusions:

  • Elevated cognitive reserve can buffer the impact of hippocampal atrophy on neuropsychiatric symptoms, independent of overall cognition.
  • These findings suggest CR offers protective benefits that extend beyond cognitive function to behavioral outcomes.
  • Further longitudinal research is recommended to explore domain-specific CR effects and functional imaging correlates.