Association of Accelerated Biological Age in Midlife with Cardiovascular Events, Dementia, and All-Cause Mortality in the Framingham Offspring Study

Accelerated biological age (ABA) better capture the aging process than chronological age (CA) and has been linked to adverse health outcomes, but long-term associations remain unclear. We modeled ABA using anthropometric and biochemical biomarkers across three examination cycles (1991–2001) in 3046 Framingham Offspring Study participants. Stratified by sex, BA was estimated using the Klemera and Doubal method with principal components and categorized as accelerated (> 1SD), concordant (± 1SD), or decelerated (DBA; < -1SD) based on standardized residuals from CA. Multivariable-adjusted time-dependent Cox and competing risk models were used to relate ABA with cardiovascular disease (CVD), dementia, and mortality. Over a median follow-up of 26 years (maximum 31), participants (mean age 55 years, 55% women) experienced 713 CVD events, 265 dementia cases, and 1105 deaths. Compared with DBA, men with ABA had higher risks of CVD (HR 1.6; 95% CI 1.07–2.28; p = 0.02) and death (HR 2.3; 95% CI 1.73–3.18; p < 0.0001). Women with ABA had higher risks of CVD (HR 1.8; 95% CI 1.24–2.64; p = 0.002), dementia (HR 2.1; 95% CI 1.03–4.32; p = 0.04), and death (HR 1.8; 95% CI 1.27–2.54; p = 0.0009). Accelerated midlife BA was associated with increased risk of adverse outcomes, particularly dementia in women, supporting the importance of healthy multisystem aging over the life course.