Background
Modifiable risk factors account for a substantial proportion of dementia cases and represent important targets for prevention. However, previous studies have often focused on a limited range of risk factors and have rarely examined whether their associations with dementia differ according to sex and age at onset. Objectives: To investigate sex- and age-specific associations between modifiable risk factors and incident Alzheimer's disease dementia using a nationwide population-based cohort in South Korea.
Methods
We conducted a retrospective cohort study using the National Health Information Database of the Korean National Health Insurance Service. Among individuals who participated in the National Cancer Screening Program in 2006 and underwent general health examinations in 2004, 2006, and 2008, 599,306 adults aged 40–79 years were included. Participants were followed from 2010 to 2019 after applying pre- and post-screening washout periods. Incident Alzheimer's disease dementia was defined using ICD-10 codes F00 or G30. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Analyses were stratified by sex and age group to distinguish early-onset Alzheimer's disease dementia (EOAD) and late-onset Alzheimer's disease dementia (LOAD). During the 10-year follow-up period, dementia risk profiles differed substantially according to sex and age at onset. Lower educational attainment was consistently associated with increased dementia risk across all groups. Current smoking and physical inactivity were significant risk factors for dementia in both sexes, whereas underweight status was associated with an increased risk of LOAD. Among chronic conditions, diabetes, hypertension, and depression elevated dementia risk, with depression demonstrating the strongest association, particularly for EOAD (males: HR = 3.61, 95% CI: 2.63–4.96; females: HR = 1.83, 95% CI: 1.46–2.29). Sensory and functional impairments, including hearing loss, visual loss, physical disability, and traumatic brain injury, were also associated with increased dementia risk, although the magnitude and significance of these associations varied by sex and age group. The predictive performance of the models was acceptable, with C-statistics ranging from 0.6784 to 0.7803.
Conclusions
The associations between modifiable risk factors and incident Alzheimer's disease dementia exhibited distinct sex- and age-specific patterns. These findings highlight the importance of tailored dementia prevention strategies that account for differences in demographic characteristics and risk factor profiles. Targeted interventions addressing modifiable risk factors may contribute to reducing the future burden of dementia at both individual and population levels.

Although there is a genetic component to primary open-angle glaucoma (POAG) susceptibility, few studies have investigated interactions between genetic and environmental factors. We aimed to quantify the familial risk of POAG and estimate disease risk among individuals with a positive family history and either hypertension or hyperglycemia, as well as assess their interactions. Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 6,217,057 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% confidence intervals (CIs) which compare the risk of individuals with and without affected FDRs. Disease risk was estimated among individuals with both a positive family history and hypertension or hyperglycemia, and interactions were assessed on an additive scale. Individuals with an affected parent had a 3.13-fold (95% CI 2.74 –3.58) increased risk of disease compared to those with unaffected parents. Individuals with affected father, mother, or both affected parents showed HRs (95% CI) of 3.50 (2.86 –4.30), 2.87 (2.41 –3.44) and 4.88 (1.83 –12.98), respectively. Familial risk adjusted for lifestyle factors decreased slightly (HR 3.14), suggesting that genetic component is the predominant driver in the familial aggregation. Individuals with a positive family history and either hypertension or hyperglycemia had a markedly elevated risk of disease, with HRs of 3.42 (95% CI 2.49 –4.69) and 3.27 (95% CI 2.15 –4.97), respectively. Hypertensive or hyperglycemic individuals with a positive family history may be considered a high-risk group and glaucoma screening may be considered.