The impact of slope-adjusted visit-to-visit body mass index variability on early dementia risk prediction.

Abstract

Previous studies have not typically separated body mass index (BMI) slope and variability as distinct constructs when examining dementia risk. This study assessed the association between the slope-adjusted visit-to-visit BMI variability and dementia risk. We conducted a retrospective cohort study using Japanese national health insurance data (2015-2023) of individuals aged 50-74 years who underwent five annual health checkups. BMI variability was assessed using the slope-adjusted standard deviation (SD) to account for underlying temporal trends. The proxy outcome for dementia was antidementia drug initiation, analyzed using Fine-Gray competing risk models, accounting for death as a competing risk. During the mean 2.17 ± 1.19 years of follow-up among 303,042 participants (mean age: 66.6 years, men: 38.6%), antidementia drugs (predominantly donepezil: 67.4%) were initiated in 665 and 2394 died. After adjusting for covariates including BMI at baseline and annual BMI change, the highest tertile of slope-adjusted BMI-SD (≥0.50 kg/m²) was significantly associated with increased dementia risk compared with the lowest tertile (≤0.31 kg/m²). Annual BMI change showed a U-shaped association with dementia risk, with pronounced elevation in the first tertile (BMI decline ≤-0.31%, hazard ratio: 1.60, 95% confidence interval: 1.32-1.93). In the basic model including baseline covariates except BMI at baseline, there was no significant difference in the C-statistics improvements when BMI at baseline or adding slope-adjusted BMI-SD (+0.0147 vs +0.0146) were added, while the greatest C-statistics improvement was observed when BMI decline ≤-0.31% was added. The association between the highest slope-adjusted BMI-SD tertile and dementia risk was stronger in females than males (P for interaction = 0.0039). Slope-adjusted visit-to-visit BMI variability is independently associated with dementia risk, particularly among females, while BMI decline patterns are strong risk factors of dementia. Incorporating longitudinal monitoring of visit-to-visit BMI variability into routine dementia screening may be beneficial.