Cognitive reserve, genetic risk, and lifestyle in the incidence and progression of type 2 diabetes: A large community‐based longitudinal study

AIMS: While high cognitive reserve (CR) is associated with a reduced risk of dementia, its potential link to type 2 diabetes (T2D) has not been well established. This study aimed to investigate the relationship between CR and both the incidence and trajectory of T2D, and to assess whether these associations differ depending on genetic predisposition and lifestyle behaviours. MATERIALS AND METHODS: We included 284 267 UK Biobank participants free of T2D at baseline. CR was quantified using a composite score derived from education, TV viewing time, occupation, confiding frequency, social contact, and leisure activities, and categorised into low, moderate, and high levels. Using multi-state models, we assessed associations of CR with incident T2D, complications, and mortality, estimating hazard ratios (HR). RESULTS: A total of 10 484 participants developed T2D, of whom 2608 experienced complications and 15 363 died, over a median follow-up of 13.7 years. Higher CR was consistently associated with lower risks across key stages in the T2D trajectory, including the development of T2D (HR: 0.58; 95% CI: 0.55-0.61), progression to complications (HR: 0.80; 95% CI: 0.68-0.82), and transition from complications to all-cause mortality (HR: 0.66; 95% CI: 0.52-0.83). Individuals with both low CR and high genetic risk had a substantially increased risk of T2D (HR: 5.54; 95% CI: 5.00-6.13) compared with those with high CR and low genetic risk. CONCLUSIONS: High CR is linked to better outcomes in T2D. Our results indicate that the positive impact of CR extends beyond dementia, also benefiting T2D management.