Work

Long‐term changes in cardiorespiratory fitness and incidence of Alzheimer's disease and related dementias among US Veterans

Year: 2025

Type: article

Abstract: INTRODUCTION Alzheimer's disease and related dementias (ADRD) remain a leading cause of morbidity and mortality. Poor cardiorespiratory fitness (CRF) has been identified as a potential risk factor for ADRD. Since CRF is a modifiable risk factor, we evaluated the association between CRF changes over time and ADRD risk. METHODS Our cohort consisted of US Veterans (mean age 60.7±9.0 years; male, n = 128,749; and female, n = 5,421). All completed two standardized exercise treadmill tests (ETT) between 2000 and 2017, at least 1 year apart (mean 3.5±2.7 years), with no evidence of ADRD at the time of both ETTs. We assigned participants to one of three age‐ and gender‐specific CRF categories based on peak metabolic equivalents (METs) achieved during the initial ETT and five categories based on CRF changes at the final ETT. Cox proportional hazard models adjusted for age, comorbidities, and medications were used to evaluate ADRD risk across CRF categories. RESULTS During the up to 15.0 years of follow‐up (mean 7.2 years; interquartile range [IQR] 4.3–9.9 years), totaling 966,337 person‐years, 10,699 ADRD cases occurred (11.1 events/1000 person‐years). Compared to the Low‐fit group, ADRD risk decreased progressively with increased CRF and was 22% lower (hazard ratio [HR] 0.78; 95% confidence interval [CI]: 0.75‐0.81; p <0.0001) for Moderate‐fit individuals and 30% lower (HR 0.70, 95% CI: 0.67–0.73; p <0.0001) for High‐fit individuals. Compared to Low‐fit individuals with no CRF change, an increase of 0.1–<2.0 METs was associated with a 13% lower ADRD risk (HR 0.87, 95% CI 0.79–0.95; p <0.0001), while an increase of ≥2.0 METs was associated with a 24% lower risk (HR 0.76, 95% CI 0.70–0.83; p <0.0001). CONCLUSION We observed an inverse and independent association between CRF and ADRD risk. An improvement in CRF of approximately ≥1.0 MET led to a lower risk of ADRD in Low‐fit individuals. These findings may have considerable clinical and public health significance in reducing ADRD risk. Highlights Poor cardiorespiratory fitness (CRF) has been identified as a potential risk factor for Alzheimer's disease and related dementias (ADRD). Thus, we assessed the potential impact of changes in CRF over time on ADRD risk. CRF changes reflected inverse and proportional changes in ADRD risk. Low‐fit individuals who improved their CRF by ≥0.1 metabolic equivalents (METs) had a 13%–24% lower ADRD risk. Conversely, a decline in CRF by ≥2.0 METs was associated with a 14% increased ADRD risk among Moderate‐fit and a 18% increase among High‐fit individuals.

Source: Alzheimer s & Dementia Translational Research & Clinical Interventions

DOI: 10.1002/trc2.70171