Supplementary Material for: Sex-Specific Modifiable Factors for Incident Late-Onset Dementia in the Geographic Context: A Longitudinal Comparative Analysis of Multicohort Studies Across 19 Countries

Background: Evidence regarding sex-specific risk factors across various regions contributing to late-onset dementia (LOD) incidence remains limited. We sought to explore the common influencing factors within the same sex across various regions. Methods: This cohort study used four independent samples across 19 countries between 2010 and 2020: the China Health and Retirement Longitudinal Study (CHARLS), the Survey of Health, Ageing and Retirement in Europe (SHARE), the Health and Retirement Study (HRS) in the United States, and the English Longitudinal Study of Ageing (ELSA). Feature selection was performed using LASSO and Boruta models. Hazard ratios (HRs) for selected variables and LOD or late-onset Alzheimer's disease (LOAD) were estimated using the Cox model. Results: We included 39,439 participants (56.3% female) aged 65 years and older without dementia at baseline. During the follow-up period, 3,548 patients (59.2% female) with LOD were recorded. Females had a 21% lower risk (pooled HR: 0·79 [0.69-0.89]) of developing LOD than males. While age was identified as a common risk factor across all female populations in four cohorts, no common risk factor was found among male populations. Current drinkers served as a consistent modifiable factor for females in 18 countries (from North America and Europe) other than China, and for males in Europe (HR: 0.62 [0.47–0.82]). An additive interaction between current drinking and age was observed in females but not in males. The association between drinking alcohol frequency and LOD was inconsistent among females in the HRS and the ELSA. No significant associations between alcohol consumption and LOAD were found in the HRS and the ELSA. Conclusions: These findings suggest that moderate alcohol intake may reduce the risk of LOD among younger-old females in North America and Europe, as well as males in Europe.