Background Lifestyle behaviours have been linked to dementia incidence, but their cumulative impact on dementia and the mechanisms through which they exert their impact remain poorly understood. This study investigated the association of co-occurring lifestyle behaviours with dementia incidence and the mediating role of systemic inflammation in this association.

Methods The sample comprised 3,131 participants (55.2% female) from the English Longitudinal Study of Ageing aged 52-92 years at baseline (2008/09). Self-reported baseline lifestyle behaviours (alcohol intake, fruit and vegetable consumption, smoking, physical activity, sleep duration, social engagement, and cognitive activity) were summed to derive an index of lifestyle behaviours, ranging from 0 to 7, with higher scores denoting a higher number of health-risk behaviours. Incident dementia cases (n= 130, 4.2%) were identified through doctor-diagnosed dementia, informant interviews, and health records between 2014/15 and 2018/19. Systemic inflammation was measured through fasting plasma concentrations of C-reactive protein (CRP) in 2012/13.

Results Binary logistic regression models indicated that the odds of subsequent dementia increased by 1.21 for each additional health-risk behaviour (95% confidence intervals: 1.05, 1.39, p= .007) after adjusting for age, sex, ethnicity, wealth, education, marital status, body mass index, coronary heart disease, hypertension, stroke, depression, and baseline CRP levels. However, this association was not mediated by CRP.

Conclusion Co-occurring health-risk behaviours were associated with higher dementia incidence up to 10 years later, underscoring the importance of modifying health-risk behaviours for the prevention of dementia. Systemic inflammation did not explain the association between behaviours and dementia. While systemic inflammation was not found to explain the association between behaviours and dementia, focusing on health-promoting behaviours remains paramount. By prioritising a healthy lifestyle, individuals can proactively safeguard their cognitive health and overall well-being. Our findings emphasise the importance of proactive health management and empower individuals to take actionable steps to reduce their risk of dementia through lifestyle modifications.