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Social factors like discrimination did not alter TOMM40 gene effects on cognitive decline. However, discrimination predicted faster decline in APOE-ε4+ carriers, suggesting genetic vulnerability to social stressors.

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Area of Science:

  • Neuroscience
  • Genetics
  • Social Epidemiology

Background:

  • Social determinants like discrimination and loneliness are linked to cognitive decline in Black Americans.
  • TOMM40 gene variants, particularly TOMM40-'523-S, interact with APOE genotype and influence cognitive trajectories.
  • The combined impact of social factors and TOMM40-'523-S on cognition in Black older adults remains understudied.

Purpose of the Study:

  • To investigate whether social factors (discrimination, loneliness) modify the association between TOMM40-'523-S genotype and cognitive decline.
  • To examine the interplay between TOMM40-'523-S, APOE genotype, and social factors in predicting cognitive trajectories in a cohort of Black older adults.

Main Methods:

  • Utilized linear mixed-effects models on data from 436 dementia-free non-Hispanic Black participants.
  • Assessed the effects of TOMM40-'523-S copies (0, 1, or 2) within APOE genotypes (ε3/ε3 or ε4+) and social factors (discrimination, loneliness) on global and domain-specific cognition.
  • Controlled for age, education, sex/gender, and time from baseline over an average of 9.5 years of follow-up.

Main Results:

  • Social factors did not mediate the relationship between TOMM40-'523-S and cognitive decline.
  • APOE-ε4+ carriers experiencing discrimination showed accelerated decline in working memory and perceptual speed.
  • Loneliness was not associated with cognitive decline, but baseline effects of discrimination and loneliness varied by APOE genotype.

Conclusions:

  • Social factors do not influence the TOMM40-'523-S effect on cognitive decline.
  • Discrimination predicts cognitive decline specifically in APOE-ε4+ carriers, highlighting their heightened vulnerability.
  • Baseline cognition is differentially affected by social factors based on APOE genotype.