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Modifiable lifestyle factors have been shown to promote healthy brain ageing. However, most studies to date have focused on one factor at a time. Given that lifestyle factors do not occur in isolation, multivariable analyses may provide a more realistic model of the impact of modifiable lifestyle factors on brain ageing. We examined the relationship between nine lifestyle factors and seven MRI-derived indices of brain structure using canonical correlation analysis (CCA). The resulting covariance pattern was then explored with Bayesian regressions. CCA analyses were first completed in a Danish cohort of older adults (n = 251) and then replicated in an independent cohort from the United Kingdom (n = 668). In both cohorts, the latent lifestyle factors were positively associated with the latent structural brain measures (UK: r = 0.37, p < 0.001; Denmark: r = 0.27, p < 0.001). In the cross-validation study, the correlation between lifestyle-brain latent factors was r = 0.10, p = 0.008. However, the pattern of univariate associations differed between datasets. Taken together, these findings suggest that lifestyle interventions would benefit from baseline characterisation and tailoring towards the study sample.

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