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Related Experiment Video

Updated: Jan 8, 2026

Determining Soil-transmitted Helminth Infection Status and Physical Fitness of School-aged Children
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Public Health.

Samantha Lg Paço1, Shea J Andrews2, Michel Satya Naslavsky3

  • 1Universidade de São Paulo, São Paulo, Sao Paulo, Brazil.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Polygenic risk scores (PRS) show varying predictive power for cognitive decline in Brazilian and European elderly. Genetic ancestry significantly influences Alzheimer's disease risk and cognitive performance across diverse populations.

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Area of Science:

  • Genetics
  • Neuroscience
  • Population Health

Background:

  • Alzheimer's disease (AD) is associated with cognitive decline, with genetic factors like the APOE4 allele increasing risk.
  • Polygenic risk scores (PRS) aggregate genetic variants to predict AD susceptibility.
  • This study investigates PRS models in Brazilian (SABE) and European (ADNI) populations to understand genetic influences on cognitive impairment.

Purpose of the Study:

  • To evaluate the effectiveness of different Polygenic Risk Score (PRS) models in predicting cognitive impairment.
  • To examine the influence of genetic ancestry and the APOE4 allele on cognitive performance in admixed and European populations.
  • To compare PRS model performance across the SABE and ADNI datasets.

Main Methods:

  • Generated PRS using PRSice-2, including Bel, Kunkle, Kunkle-AFR, and PRS_SUM models.
  • Analyzed data from the SABE (Brazilian, n=1,103) and ADNI (European, n=785) cohorts.
  • Employed linear regression with bootstrapping, controlling for age, sex, education, APOE4 status, and local ancestry.

Main Results:

  • In SABE, age negatively impacted cognition, while education positively influenced it. APOE4 showed a minor effect, more pronounced in individuals of European ancestry. PRS models explained 26.6-26.8% of variance.
  • Local ancestry analysis in SABE revealed higher homozygosity in European and East Asian ancestries.
  • In ADNI, APOE4 significantly affected MMSE scores. The Kunkle PRS model (R2=0.155) showed higher predictive power than Kunkle-AFR (R2=0.131) for cognitive variability.

Conclusions:

  • PRS models demonstrate varied predictive capabilities for cognitive performance across different ancestral populations.
  • Local ancestry is crucial for understanding cognitive impairment in admixed populations like the SABE cohort.
  • Genetic factors, including PRS and APOE4, interact complexly with ancestry to influence cognitive health in aging populations.