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Related Experiment Video

Updated: Sep 11, 2025

Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
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Alzheimer's Polygenic Risk and Clinical Severity Manifest in Greater Cognitive Intra-Individual Variability.

Chin Hong Tan1,2

  • 1Psychology, School of Social Sciences, Nanyang Technological University, Singapore, Singapore.

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|August 19, 2025
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Summary

Higher polygenic risk and cognitive intra-individual variability (IIV) are linked to dementia severity. These factors, along with apolipoprotein E (APOE) ε4, predict cognitive IIV and clinical decline in aging individuals.

Keywords:
Alzheimer’s diseaseApolipoprotein ECognitionDementiaNeuropsychologyPolygenic risk score

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Area of Science:

  • Neuropsychology
  • Genetics
  • Gerontology

Background:

  • Cognitive intra-individual variability (IIV) is a key neuropsychological marker indicating performance fluctuations across cognitive domains.
  • Understanding factors influencing IIV is crucial for comprehending cognitive aging and neurodegenerative diseases.

Purpose of the Study:

  • To investigate the association between clinical severity, apolipoprotein E (APOE) ε4 carrier status, and polygenic risk with cognitive IIV.
  • To examine the synergistic effect of polygenic risk and cognitive IIV on clinical severity.

Main Methods:

  • Analysis of data from up to 24,248 participants (mean age 72) from the National Alzheimer's Coordinating Center (NACC).
  • Multiple regression analysis was employed, controlling for age, sex, and education.

Main Results:

  • Disease severity, APOE ε4 carrier status, and higher polygenic risk were all significantly associated with increased cognitive IIV.
  • A significant interaction was found between polygenic risk and cognitive IIV in influencing clinical severity, independent of APOE ε4 status.

Conclusions:

  • Elevated polygenic risk and increased cross-domain cognitive variability are implicated in dementia.
  • These factors may jointly contribute to clinical decline in individuals with dementia.