Association of Predicted Visceral Fat Percentage With Dementia Risk in Older Adults: The Role of Genetic Risk and...

Obesity is a modifiable dementia risk factor, but body mass index does not account for fat distribution, particularly visceral fat, which is more strongly linked to metabolic and cardiovascular health. Despite its relevance, research on visceral fat and dementia is limited, especially in large-scale prospective studies. The aim of this study was to assess the association between visceral fat and dementia risk, its interaction with genetic predisposition, and the impact of healthy lifestyle adherence.

Using data from the UK Biobank (UKB) cohort, we computed baseline, sex-specific visceral fat percentage (VFP), defined as the ratio of visceral fat mass to total body fat mass. Nonlinear associations between VFP and incident dementia were initially assessed using restricted cubic splines. The relationship between VFP and incident dementia was further examined using Cox proportional hazard models. In addition, stratified and interaction analyses were conducted to assess dementia incidence across VFP levels, lifestyle factors, and genetic risk.

The study included 63,042 women (mean age: 63.96 years) and 74,001 men (64.20 years) aged 60 years and older from the UKB, with a median follow-up of 14.07 years for men and 14.09 years for women. During follow-up, 2,805 men and 1,893 women developed dementia. A U-shaped association between VFP and dementia risk was observed in both sexes. In men, each SD increase in VFP below the median value of 8.1% was associated with a reduced risk of dementia (HR: 0.90, 95% CI 0.85-0.96), whereas above the median, the risk increased (1.06, 1.00-1.11). Similarly, in women, below the median VFP value of 3.1%, each SD increase was linked to a decreased dementia risk (0.89, 0.83-0.96), and above the median, the risk increased (1.14, 1.07-1.22). No significant interactions were found between VFP and genetic risk or lifestyle factors.

Among nondemented, community-dwelling older Britons, atypical VFP was associated with higher dementia risk in both sexes. The lack of interaction between VFP and genetic risk highlights the complexity of dementia pathogenesis. In addition, a healthy lifestyle may mitigate the dementia risk associated with atypical VFP levels.