Age- and sex-specific modifiable risk factor profiles of dementia: evidence from the UK Biobank

Dementia constitutes a worldwide concern. To characterize the age- and sex-specific modifiable risk factor profiles of dementia, we included 497,401 UK Biobank participants (mean age = 56.5 years) without dementia at baseline (2006-2010) and followed them until March 2021. Cox proportional hazard models were used to estimate the age- and sex-specific hazard ratios (HRs) of incident dementia associated with socioeconomic (less education and high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, physical inactivity, and unhealthy sleep duration), and health condition factors (hypertension, diabetes, cardiovascular diseases, and depressive symptoms). We also calculated the population attributable fractions (PAFs) of these factors. During follow-up (mean = 11.6 years), we identified 6564 dementia cases. HRs for the risk factors were similar between the sexes, while most factors showed stronger associations among younger participants. For example, the HRs of smoking were 1.74 (95% CI: 1.23, 2.47) for individuals aged < 50 years, and 1.18 (1.05, 1.33) for those aged ≥ 65 years. Overall, 46.8% (37.4%, 55.2%) of dementia cases were attributable to the investigated risk factors. The PAFs of the investigated risk factors also decreased with age, but that for health condition risk factors decreased with lower magnitude than socioeconomic and lifestyle risk factors. The stronger associations and greater PAFs of several modifiable risk factors for dementia among younger adults than older participants underscored the importance of dementia prevention from an earlier stage across the adult life course.