How much can biomarkers explain sociodemographic inequalities in cognitive dysfunction and cognitive impairment? Results from a machine learning model in the Health and Retirement Study

J Alzheimers Dis. 2025 Jul;106(1):54-68. doi: 10.1177/13872877251338063. Epub 2025 May 5.

Abstract

BackgroundBiomarkers may be pathways by which social adversity affects cognitive aging and Alzheimer's disease and related dementias (ADRD) risk.ObjectiveHow much variance in cognitive dysfunction and cognitive impairment onset do blood-based and physiological biomarkers provide above and beyond easily attainable sociodemographic variables, and how much can biomarkers explain differences in cognitive functioning and ADRD by sociodemographic variables?MethodsWe utilize machine learning to generate measures of predicted cognitive dysfunction and cognitive impairment incidence based on 91 biomarkers, identify the relative importance of each biomarker, and examine how much these biomarkers mediate sociodemographic differences.ResultsMarkers related to cellular aging, neurodegeneration, diet and nutrition, immune functioning, and lung function were identified as important. Biomarkers mediated 47.2-77.3% of the variance associated with age, 22.7-35.2% of racial/ethnic differences in cognitive dysfunction, and 12.5-17.6% of educational differences.ConclusionsBiomarkers provide the potential to understand pathways linking sociodemographic characteristics to cognitive functioning and health. Future research should consider additional biomarkers and evaluate the specific systems that put people at risk for cognitive impairment.

Keywords: Alzheimer’s disease; biomarkers; machine learning; multiomics; sociodemographic factors.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers* / blood
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / epidemiology
  • Cognitive Dysfunction* / psychology
  • Female
  • Humans
  • Machine Learning*
  • Male
  • Middle Aged
  • Sociodemographic Factors
  • Socioeconomic Factors

Substances

  • Biomarkers