Cardiorespiratory fitness and risk of Alzheimer's disease and related dementias among American veterans

Cardiorespiratory fitness (CRF) is associated with improved health and survival. Less is known about its association with Alzheimer's disease and related dementias (ADRD).We identified 649,605 US veterans 30 to 95 years of age and free of ADRD who completed a standardized exercise tolerance test between 2000 and 2017 with no evidence of ischemia. We examined the association between five age- and sex-specific CRF categories and ADRD incidence using multivariate Cox regression models.During up to 20 (median 8.3) years of follow-up, incident ADRD occurred in 44,105 (6.8%) participants, with an incidence rate of 7.7/1000 person-years. Compared to the least-fit, multivariable-adjusted hazard ratios (95% confidence intervals) for incident ADRD were: 0.87 (0.85-0.90), 0.80 (0.78-0.83), 0.74 (0.72-0.76), and 0.67 (0.65-0.70), for low-fit, moderate-fit, fit, and high-fit individuals, respectively.These findings demonstrate an independent, inverse, and graded association between CRF and incident ADRD. Future studies may determine the amount and duration of physical activity needed to optimize ADRD risk reduction.