# Sex-difference in the association between Triglyceride-Glucose (TyG) index and dementia

## TL;DR

This study finds that high insulin resistance, measured by the TyG index, is linked to a higher risk of certain dementias in older women but not men.

## Contribution

The study reveals a sex-specific link between insulin resistance and dementia subtypes, particularly in females.

## Key findings

- High TyG index in females is associated with increased odds of mild cognitive impairment, vascular dementia, and mixed dementia.
- These associations remain significant after adjusting for age, smoking, cholesterol, and comorbidities.
- No significant association was found between TyG index and Alzheimer’s disease in females or any dementia subtype in males.

## Abstract

This study aims to evaluate the association between the insulin resistance as assessed by Triglyceride-Glucose (TyG) index and dementia and to determine whether this relationship varies by sex.

We assessed TyG index in older patients admitted to an Italian Memory Clinic with different cognitive status: 335 (71% females-F) participants with Alzheimer’s disease (AD), 99 (61% F) with vascular dementia (VAD), 301 (67% F) with mixed dementia (MIXED: AD + VAD), 442 (57% F) with mild cognitive impairment (MCI), and 173 cognitively healthy controls (61% F).

We found that only in females high TyG index was associated with a greater probability of receiving a diagnosis of MCI (odd ratio - O.R.: 1.91, 95% confidence interval - C.I.: 1.08–3.34), VAD (O.R.: 2.23; 95% C.I.: 1.10–4.51), and MIXED (O.R.: 1.92, 95% C.I.: 1.10–3.33), but not AD (O.R.: 1.07, 95% C.I.: 0.63–1.85). Notably, these associations remained significant in a multi-adjusted model, including age, smoking, total cholesterol and comorbidities.

Our findings suggest that insulin resistance may be a risk factor for dementia with a cerebrovascular component, but only in older females.

The online version contains supplementary material available at 10.1007/s40200-025-01744-z.