Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial

OBJECTIVE: The objective of this study was to investigate whether a 5-year exercise intervention and change in peak oxygen uptake ([Formula: see text] ) is associated with cognitive function in older adults. METHODS: Nine hundred and forty-five participants (48% women, mean age at study end 78.2 ± 2.02 years) from the Generation 100 Study were randomized 2:1:1 to a control group, moderate-intensity continuous training or high-intensity interval training twice weekly for 5 years. Peak oxygen uptake was measured using ergospirometry at baseline and after 5 years. Global cognition and mild cognitive impairment (MCI) were assessed with the Montreal Cognitive Assessment scale (MoCA) after 5 years. RESULTS: Compared to the control group, the combined moderate-intensity continuous training plus high-intensity interval training (ExComb) group did not have significantly different cognitive scores (beta value 0.26, 95% confidence interval [CI] − 0.17, 0.69) or odds of MCI (odds ratio 0.86, 95% CI 0.66, 1.13). Men in the ExComb group had 0.80 points higher MoCA (95% CI 0.21, 1.40) and 32% lower odds of MCI compared with male controls (95% CI 0.47, 0.99), with no such findings in women. In the total sample, each 1 metabolic equivalent of task increase in [Formula: see text] corresponded to 0.46 points higher MoCA (95% CI 0.25, 0.67) and 27% lower odds of MCI (95% CI 0.63, 0.85). Compared to [Formula: see text] stable, participants whose [Formula: see text] increased did not have significantly different cognitive scores (beta value 0.24, CI − 0.68, 1.15) or odds of MCI (odds ratio 0.70, 95% CI 0.36, 1.34), whereas participants whose [Formula: see text] decreased had 0.64 points lower MoCA (95% CI − 1.15, − 0.14) and 35% higher odds of MCI (95% CI 0.98, 1.87). CONCLUSIONS: Overall, exercise was not significantly associated with cognition among older adults. However, maintaining or increasing [Formula: see text] appeared to benefit cognition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40279-021-01608-5.