# Insulin resistance (TyG index) and body mass index as metabolic biomarker combined with ApoE genotype to diagnose Alzheimer’s disease

## TL;DR

This study explores how ApoE genotype interacts with metabolic factors like insulin resistance and BMI to affect cognitive function in Alzheimer’s disease patients.

## Contribution

The study identifies a novel interaction between ApoE ε4 genotype and metabolic biomarkers in influencing cognitive decline in Alzheimer’s disease.

## Key findings

- ApoE ε4 carriers had significantly lower BMI and higher TyG index compared to non-carriers.
- ApoE ε4’s negative effect on cognition was partially mediated through BMI reduction and TyG elevation.
- Metabolic dysregulation linked to ApoE ε4 may contribute to cognitive decline in Alzheimer’s disease.

## Abstract

Growing evidence suggests that both ApoE genotype and metabolic disturbances including insulin resistance (IR) and obesity constitute risk factors for Alzheimer’s disease (AD). However, large-scale studies investigating whether ApoE genotype interacts with metabolic abnormalities to indirectly impair cognitive function in AD remain scarce.

This cross-sectional study aimed to explore the associations between ApoE genotype, metabolic disturbances [IR assessed by triglyceride-glucose (TyG) index and body mass index (BMI)], and cognitive function in AD patients.

We analyzed 1,162 clinically diagnosed probable AD patients from the Cognitive Impairment Clinic at Tianjin Huanhu Hospital. Participants were categorized by ApoE ε4 carrier status. Metabolic parameters were evaluated using the TyG index and BMI. Mediation effect models were employed to assess the relationships between ApoE genotype, metabolic indices, and cognitive function.

ApoE ε4 carriers exhibited significantly lower BMI (P < 0.001) and higher TyG index (P < 0.001) compared to non-ApoE ε4 carriers. Significant TyG index elevation in ApoE ε4 carriers was observed in AD patients with Mini-Mental State Examination (MMSE) > 20 (P = 0.0036) and MMSE 10–20 (P = 0.009). Mediation analysis revealed that ApoE ε4 exerted 73.4% of its negative effect on cognition through direct pathways, while 9.7 and 16.9% were mediated through BMI reduction and TyG elevation, respectively.

ApoE ε4 carriers demonstrate a distinct metabolic profile characterized by lower BMI and elevated TyG index, associated with poorer cognitive performance. Our findings suggest that ApoE ε4 may indirectly influence AD cognition through metabolic pathways, highlighting early interventions targeting ApoE-related metabolic dysregulation as potential strategies to delay AD progression.