Fig. 4. The longitudinal rate of change in R1 and R2 in the cognitively unimpaired population.

A Longitudinal brain association studies show that the R1 dimension exhibits longitudinal brain volume decrease in widespread brain regions, whereas the R2 dimension displays longitudinal brain volume decrease in the focal medial temporal lobe. We first derived the rate of change of the 119 GM ROIs and the R1 and R2 dimensions using a linear mixed effect model; a linear regression model was then fit to the rate of change of the ROIs, R1, and R2 to derive the beta coefficient value of each ROI. A negative value denotes longitudinal brain changes with a negative coefficient of the rate of change in the linear regression model. p value and effect sizes (r, Pearson’s correlation coefficient) are presented in Supplementary eTable 8. The brain maps denote the signed p value, and the range of r for each dimension is also shown. Of note, the sample size (N) for R1 and R2 is the same for each ROI. B The rate of change, not the baseline measurement, in the two dimensions is negatively associated with the CSF level of Aβ42 (Bonferroni correction for the 45 variables: −log₁₀(p value) >2.95). The rate of change in the R2 dimension, not the R1 dimension, was marginally (−log₁₀(p value) >1.31) associated with the CSF level of tau and p-tau, and APOE ε4. All other clinical associations are presented in Supplementary eTable 9. The gray-colored circle lines indicate different p value thresholds in both directions (Bonferroni correction for the 45 variables: −log₁₀(p value) >2.95 and the nominal p value threshold: −log₁₀(p value) >1.31). A positive/negative −log₁₀(p value) value indicates a positive/negative correlation (beta). Transparent dots represent the associations that do not pass the nominal p value threshold [log₁₀(p value) = 1.31]; the blue-colored dots and red-colored dots indicate significant associations [log₁₀(p value) >1.31] for the R1 and R2 dimensions, respectively.