Objectively Measured Cardiorespiratory Fitness as a Potential Biomarker for Alzheimer’s Disease Risk in Older Adults: Evidence from the Generation 100 Study
Daniel Estil Brissach, Helene Haugen Berg, Dorthe Stensvold, Emma M. L. Ingeström, Tara L. Walker, Jari A. Laukkanen, Tommi Vasankari, Sigrid Botne Sando, Atefe R. Tari, Ulrik WisløffPurpose:
Cardiorespiratory fitness is a modifiable physiological trait linked to dementia risk, but whether objectively measured peak oxygen uptake (VO 2peak ) and short-term changes fitness in older adults associates with Alzheimer’s disease (AD) remains unknown. We examined whether baseline levels and one-year changes in VO 2peak were associated with subsequent risk of AD in older adults.
Methods:
This prospective cohort study included participants from the Generation 100 Study. VO 2peak was measured at baseline (2012–13) and 1-year follow-up. Participants were categorized as unfit (<80% of the sex-specific mean VO 2peak ), moderately fit (80–99%), or fit (≥100%). Incident AD was identified through national health registries, hospital records, and the Norwegian Prescribed Drug Registry. Cox proportional hazards models estimated associations between VO 2peak and incident AD.
Results:
A total of 1491 participants free from dementia, aged 70-77 years were included. Mean VO 2peak at baseline was 28.7 mL/kg/min. During a median follow-up of 8.7 years, 77 developed AD. Compared with unfit, moderately fit (aHR 0.54, 95% CI 0.29–0.98) and fit (aHR 0.52, 95% CI 0.29–0.93) participants had a lower AD risk. Each 1 mL/kg/min higher baseline VO 2peak was associated with a 4% lower risk of AD (HR 0.96, 95% CI 0.92–1.00). Staying above 80% of sex-specific mean VO 2peak (25.1 mL/kg/min for men and 20.9 mL/kg/min for women) was identified as a threshold of AD risk stratification of which below the risk increased substantially. Weaker associations were observed between one-year changes in VO 2peak and subsequent AD risk.
Conclusions:
Higher VO 2peak in older adults was associated with a substantially lower risk of developing AD, whereas short-term changes in fitness did not confer additional benefit. These findings suggest that entering older age with fitness >80% of sex-specific mean may be more important for reducing late-life AD risk than achieving short-term improvements after the age of 70. CRF emerged as a clinically relevant biomarker for AD, that may help stratify risk and inform preventive strategies in ageing populations.