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Public Health.

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Summary
This summary is machine-generated.

Genetic predisposition to insulin resistance (IR) is linked to better memory performance and slower cognitive decline. However, this association is influenced by comorbidities and specific genetic factors, suggesting a complex relationship.

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Area of Science:

  • Neuroscience
  • Genetics
  • Metabolic Health

Background:

  • Insulin resistance (IR) is linked to cognitive decline and dementia risk.
  • Polygenic risk scores (PRS) can identify genetic predisposition to IR.
  • Understanding the genetic liability to IR's impact on memory is crucial for dementia prevention.

Purpose of the Study:

  • To investigate the association between genetic liability to IR and memory performance.
  • To examine cross-sectional and longitudinal relationships between IR genetic risk and memory.
  • To explore how comorbidities and APOE genotype modify this association.

Main Methods:

  • A polygenic risk score (PRS) for IR was constructed using TG:HDL-C ratio from genome-wide association study data.
  • The PRS was applied to the National Alzheimer's Coordinating Center (NACC) cohort.
  • Linear regression and mixed-effects models analyzed baseline and longitudinal memory, adjusting for covariates and performing sensitivity analyses.

Main Results:

  • Higher genetic risk for IR (TG:HDL-C PRS) was associated with better baseline memory.
  • Increased genetic risk for IR correlated with slower longitudinal memory decline.
  • Associations were modified by comorbidities and APOE-ɛ4/ɛ2 non-carrier status, with reduced effect sizes when comorbidities were excluded.

Conclusions:

  • Genetic liability to IR, indicated by TG:HDL-C PRS, shows a modest but significant association with better memory and slower decline.
  • Comorbidities and APOE genotype significantly modify the relationship between IR genetic risk and memory.
  • Further research with larger cohorts is needed to elucidate the complex interplay of IR genetics, metabolism, and cognitive health.