Abstract Body: Background: The Brain Care Score (BCS) is a novel tool developed to address modifiable risk factors for the incidence of age-related brain diseases such as stroke, dementia, and late-life depression (LLD) (Fig 1). Previous data showed that a lower baseline BCS is associated with higher disease risks. This study examines the associations between longitudinal BCS changes on the incidence of these three outcomes.

Methods: UK Biobank (UKB) participants with primary care data available for longitudinal assessment of a 19-point modified BCS were included. We evaluated baseline BCS and changes over time (delta BCS), applying a weighted model to standardize changes relative to the time interval between assessments. Participants were grouped by mean delta BCS into i) improvement, ii) no change, or iii) deterioration. A logistic regression model was employed to assess the impact of BCS deterioration on outcomes, adjusting for baseline BCS, age, and sex. Multivariate Cox models evaluated associations between baseline BCS, 5-point improvement in BCS over time, and outcomes, adjusting for age and sex. Secondary analyses stratified individuals by genetic risk, using polygenic risk scores for stroke and LLD, and APOE e4 status for dementia.

Results: Among 176,693 participants (54.1% females, 45.9% males), the mean age was 56.9 years, with a median follow-up of 12 years (IQR 11-13). A total of 70.84% had improvement in BCS, 17.86% experienced deterioration and 11.2% had no significant change. Participants with BCS deterioration had an increased risk of stroke (OR 1.29; 95%CI 1.11-1.50), LLD (OR 1.60; 95%CI 1.31-1.94), and a trend for dementia (OR 1.09; 95%CI 0.93-1.27). A 5-point increase in BCS over time significantly reduced the risk of all three diseases: stroke (HR 0.73; 95%CI 0.67-0.79), dementia (HR 0.79; 95%CI 0.79-0.96) and LLD (HR 0.60; 95%CI 0.56-0.64) (Fig 2), independently of baseline BCS, age and sex. Secondary analyses demonstrated that an incremental 5-point increase in the BCS significantly reduced the risk of stroke (HR 0.61, 95%CI 0.54–0.71) and LLD (HR 0.62, 95%CI 0.55–0.70), even among individuals with the highest genetic predisposition (Fig 3).

Conclusions: Higher BCS can mitigate the risk of stroke, dementia, and LLD. Improvements in BCS over the 12-year observation period significantly lowered the incidence of these outcomes even in those with high genetic predisposition, supporting the effectiveness of the BCS as a tool for brain health.