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Background This study examined the effect of a 5-year randomized controlled exercise intervention on OI over 10 years in older adults. To test the cardiorespiratory fitness (CRF) hypothesis, which proposes that CRF, preferably measured as peak oxygen uptake (VO 2peak ), is a key mediator linking exercise to brain health, we examined the association between exercise group and OI, and VO 2peak across all participants and OI. Methods Participants (70–77 years) were randomized to 5 years of moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), or a control group asked to follow national physical activity guidelines. A longitudinal cohort of 106 participants underwent OI testing (Sniffin’ Sticks) and brain MRI at baseline and after 1, 3, 5, and 10 years. At 10 years, cross-sectional OI and MRI data were collected from an additional 326 participants, resulting in a cross-sectional cohort of 388 participants when combined with those remaining in the longitudinal cohort at 10 years. Health, exercise characteristics and VO 2peak were assessed at all timepoints in all participants. Linear mixed models assessed the effect of intervention on OI over time in the longitudinal cohort, while linear regressions examined group differences in OI at 10 years in the cross-sectional cohort. Associations between VO 2peak , self-reported exercise characteristics, and hippocampal volume with OI were assessed in both cohorts. Sensitivity analyses addressed loss to follow-up and potential selection bias. Results OI performance decreased significantly over time, with no differences between the exercise groups over 10 years or at the 10-year follow-up. There were no significant group differences in VO 2peak over time. Higher VO 2peak at baseline and 10 years was associated with better OI performance at 10 years. Hippocampal volume was positively associated with OI at the 10-year follow-up. Self-reported exercise intensity was not associated with OI, but self-reported exercise duration was significantly associated with OI up to 3-year follow-up, but not thereafter. Conclusion OI decline did not differ between the MICT, HIIT, and control groups. However, higher VO 2peak at baseline and 10 years later was associated with better OI performance. These findings suggest a direct link between VO 2peak and reduced age-related OI decline in older adults. Clinical trial registration www.clinicaltrials.gov , identifier NCT01666340.
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Reitlo et al. (2026) studied this question.
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