Table 1.
Descriptive characteristics of the sample (N = 318).
Fig 1.
Identifying brain regions in which tissue microstructure (R2) is associated with both global cognition (orange) and total daily physical activity (blue). The R2 IC identifiers along the horizontal axis refer to the 30 independent components of the transverse relaxation rate, R2. Each component captures information on tissue microstructure in a different part of the brain, as illustrated in Fig 2. The plot depicts -log10(p-values) on the vertical axis to facilitate side-by-side comparison of the entire range of p-values, including those that are very small (< .00001). Thus, taller bars reflect stronger associations, and some extend beyond the upper limits of what is displayed in this figure. The horizontal black line corresponds to the -log10 of p = .05, the nominal significance level we used to screen for candidate R2 ICs that might account for the relationship between physical activity and cognition. Of the 30 R2 ICs, two (#8 and #10, highlighted in red) were associated with both global cognition and total daily physical activity at p < .05. The linear regression model used to assess the association of R2 ICs with global cognition: Global cognition = β0 + β1*age + β2*sex + β3*education + β4*R2, with the p-value of β4 plotted in this figure. The linear regression model used to assess the association of total daily physical activity with R2 ICs: R2 = β0 + β1*age + β2*sex + β3*education + β4*physical activity, with the p-value of β4 plotted in this figure.
Fig 2.
Brain regions in which tissue microstructure (R2) partially mediated the association between physical activity and global cognition.
Of 30 independent components (ICs), R2 IC #8 and #10 were unique in that they were associated with both global cognition and total daily physical activity assessed proximate to death and mediated the association between the two, according to path analysis. This figure highlights the voxels whose R2 values contributed strongly to these two ICs. The colorized maps represent the voxelwise Z-statistic output by the FSL MELODIC ICA tool, which reflects the likelihood of a voxel belonging to the active class as opposed to background noise according to mixture modelling (see colorbar at right). For display, we applied a threshold to the IC maps based on a probability value of 0.5 of a voxel belonging to the active class. R2 IC #8: White matter and some cortical gray matter portions of the occipital and temporal lobes. R2 IC #10: Periventricular white matter extending throughout the frontal, parietal, occipital, and temporal lobes, as well as the hippocampus. The R2 values in voxels underlying these regions were negatively associated with both total daily physical activity and cognition; that is, lower R2 values (healthier tissue) were linked with higher levels of both total daily physical activity and cognitive function.
Fig 3.
Graphical depiction of path analysis with R2 ICs as mediators linking physical activity and cognition.
Standardized path coefficients are shown, along with their respective p-values. This analysis also controlled for participants’ age at death, sex, and education (not shown in this figure).
Table 2.
Mediation of the relation between physical activity and global cognition by brain tissue microstructure, in participants with and without AD dementia.
Table 3.
Mediation of the relation between physical activity and each of five cognitive domains by brain tissue microstructure.