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Basic Science and Pathogenesis.

Xian Wu1,2, Jing Zhang3, Inori Tsuchiya1,2

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Genetic and neighborhood factors jointly increase Alzheimer's disease and related dementia (ADRD) risk. Item response theory (IRT) precisely measured perceived neighborhood disorder (PND), revealing its interaction with APOE ε4 in diverse populations.

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Area of Science:

  • Genetics and Social Epidemiology
  • Neuroscience
  • Public Health

Background:

  • Alzheimer's disease and related dementia (ADRD) risk is influenced by both genetic and social factors.
  • Social factors, like neighborhood characteristics, may modify genetic risk.
  • Item response theory (IRT) offers a more precise method for constructing composite social factor scores compared to traditional summation methods.

Purpose of the Study:

  • To construct perceived neighborhood disorder (PND) scores using IRT models across diverse populations.
  • To examine the interaction between PND scores and genetic risk (APOE ε4) in ADRD.

Main Methods:

  • Utilized the All of Us dataset, creating cohorts for non-Hispanic White (NHW), Black or African American (AA), Hispanic, and Asian individuals (aged 65+).
  • Applied an IRT-based generalized partial credit model to the 13-item Ross-Mirowsky Perceived Neighborhood Disorder Scale to derive PND scores.
  • Employed logistic regression to assess the joint associations of PND scores and APOE ε4 status with dementia, adjusting for age and sex.

Main Results:

  • APOE ε4 prevalence varied across ethnic groups, being highest in AA participants (38%).
  • AA and Hispanic participants reported greater neighborhood safety disadvantages compared to NHW and Asian cohorts.
  • Increased PND scores were associated with higher odds of dementia, particularly in Hispanic individuals with one or two copies of APOE ε4.

Conclusions:

  • A significant joint association exists between APOE ε4 status, perceived neighborhood disorder, and dementia risk.
  • Future research should incorporate broader social measures, additional genetic factors, and specific ADRD subtypes to elucidate gene-environment interactions.