Figures and data
Atrophy-cognition EBM staging of AD progression.
(A) Histogram of PHG volume loss z-scores, zPHG. (B) Histogram of MMSE-decline z-scores, zMMSE. The z-scores for PHG volume loss and MMSE were standardized by the adjusted scores of the control group, and sign-inverted so that higher z-scores denote more severity. (C) Posterior probabilities, pj (k), that a subject j belongs to a stage k evaluated by the AC-EBM. (D) The ratio of subjects classified to each stage; blue: Control (CDR 0), orange: MCI due to AD (CDR 0.5), pink: mild AD dementia (CDR 1), and red: moderate AD dementia (CDR 2). (E) Distribution of the stages in the space spanned by PHG volume loss and MMSE score, in which each subject j was distinctly assigned to one of the stages with the highest posterior probability, argmaxk pj (k). The colors of the dots denote the seven stages. A star symbol denotes the probability-based weighted means of zPHG and MMSE scores at stage 4: zPHG = 1.33(±0.258) and MMSE= 26.3(±0.82). The values in parentheses denote the standard error (SE; Equation 5) of the weighted means. (F) Trajectories of PHG volume loss and MMSE score as a function of the seven stages. Probability-based weighted means (± SE) are shown. The initial and final z-scores used in the AC-EBM were: (zinitial, zfinal) = (−1.372, 3.804) for PHG volume loss and (−0.902, 12.712) for MMSE decline, respectively. (G) Progression of GM volume loss (z-scores) from stage 1 to 7. Regional GM atrophy in the predicted MCI stage (stage 4) was circled with dotted lines.
Profiles of neural synchrony as a function of the AD stages estimated by AC-EBM.
(A,B) Profiles of AEC (A) and spectral power (B) as a function of the seven stages, showing probability-based weighted means (± SE). Neural synchrony increased monotonously with AD progression in the delta-theta band and decreased monotonously in the alpha and beta bands. (C,D) Regional AEC (C) and spectral power (D) as a function of the seven stages. Deviations from the neural synchrony spatial patterns averaged over the controls are displayed. The deviations were calculated by using probability-based weighted means of the z-scores standardized by the controls. Spatial patterns in the MCI stage (stage 4) were circled with dotted lines. (E,F) Changes in neural synchrony during the preclinical stages. Regional comparisons between two stages (stages 4 vs. 1) are shown based on non-parametric tests of the weighted mean differences δz. Differences that exceed the threshold (q < 0.05) are displayed. There were no significant differences in long-range synchrony in the delta-theta band.
Trajectories of long-range neural synchrony in delta-theta, alpha, and beta-bands from SAC-EBMs.
(A,E,I) The ratio of subjects classified to each stage. The ratio was evaluated on the basis of the probabilities that each subject is assigned to each of the ten stages. (B,F,J) Trajectories of long-range synchrony, PHG volume loss, and MMSE score as a function of the ten stages, showing probability-based weighted means (± SE). The asterisks (*q < 0.05 and ***q < 0.001, FDR corrected) denote statistical significance in comparisons between stages 5 vs. 1. All pairs of stages with significant weighted-mean differences are listed in Appendix 1—table 9. Initial and final z-scores of long-range synchrony used in the SAC-EBMs were: (zinitial, zfinal) = (−1.083, 2.811), (−1.542, 1.605), and (−1.624, 1.641) in the delta-theta, alpha, and beta bands, respectively. (C,G,K) Regional AEC along the stages. The deviations from the regional patterns of the control group are displayed. The regional patterns at the onset of the MCI stage were circled with dotted lines. (D,H,L) Changes in regional patterns during the preclinical stages. Regional comparisons between two stages based on nonparametric tests of weighted mean differences δz are shown. Differences exceeding threshold (q < 0.05, FDR corrected) are displayed. The top 10 regions with significant differences are listed in Appendix 1—table 10.
Trajectories of local neural synchrony in delta-theta, alpha and beta bands from SAC-EBMs.
(A,E,I) The ratio of subjects classified to each stage. (B,F,J) Trajectories of local synchrony, PHG volume loss, and MMSE score as a function of the 10 stages, showing the weighted mean (± SE). Asterisks (***q < 0.001, FDR corrected) denote statistical significance in comparisons between stages 6 vs. 1. All pairs of stages with significant weighted-mean differences are listed in Appendix 1—table 11. Initial and final z-scores of local synchrony used in the SAC-EBMs were: (zinitial, zfinal) = (−1.329, 6.097), (−1.461, 2.866), and (−1.810, 2.784) in the delta-theta, alpha, and beta bands, respectively. (C,G,K) Regional spectral power along the stages. Departures from the regional patterns of the control group are shown. The regional patterns at the onset of the MCI stages were circled with dotted lines. (D,H,L) Changes in regional patterns during the preclinical stages. Regional comparisons between two stages are shown based on nonparametric tests of weighted mean differences δz. Differences exceeding threshold (q < 0.05, FDR corrected) are displayed. The top 10 regions with significant differences are listed in Appendix 1—table 12.
