Article Figures & Data
Figures
- Figure 1.
HC exhibits strong resting state functional connectivity with RsC. A, ROIs for functional connectivity analysis. alEC, pmEC, and HC were included from MTL, as well as RsC. B, RsC exhibits functional connectivity with HC and pmEC but not alEC. Line color and thickness correspond to t statistic of one-sample t test of β values. See Extended Data Figure 1-1 for resting state connectivity with SFG and association with medial parietal tau.
- Figure 2.
HC-RsC connectivity strength is related to medial parietal tau pathology. A, Percent of participants above tau threshold (FTP SUVR > 1.4) for each voxel in medial parietal lobe (MPL) region comprising RsC, PrC, and PCC. B, Adjusting for age, sex, and global Aβ, HC-RsC resting state functional connectivity strength is associated with mean suprathreshold tau within MPL. MPL suprathreshold tau defined as proportion of voxels above threshold within composite region. alEC-RsC (C) and pmEC-RsC (D) connectivity strength are not associated with MPL tau. Significance value for each plot corresponds to effect of each term from linear regression model. Functional connectivity (FC) strength quantified as β values from semipartial correlations between regions. Error bars indicate 95% confidence interval. See Extended Data Figure 2-1 for association between HC-RsC connectivity and tau outside of medial parietal lobe, as well as medial parietal Aβ.
- Figure 3.
HC-RsC connectivity modulates the relationship between medial temporal and medial parietal tau. Visualization of interaction between HC mean tau (partial volume corrected FTP SUVR) and HC-RsC functional connectivity strength (HC-RsC) from linear regression model (see Table 2). Medial parietal lobe (MPL) suprathreshold tau is associated with a hippocampal tau × HC-RsC interaction. Plot displays the relationship predicted by linear regression at low (10th percentile), median, and high (90th percentile) HC-RsC. Error bars indicate 95% confidence interval. See Extended Data Figure 3-1 for visualization of the same interaction effect using FTP SUVR form EC in place of HC.
- Figure 4.
Episodic memory performance is associated with the interaction of HC-RsC connectivity and medial parietal tau. Visualization of interaction between HC-RsC functional connectivity (FC) strength (β value) and medial parietal lobe (MPL) suprathreshold tau in relation to visuospatial and verbal memory, adjusting for age, sex, years of education, practice effects, and global Aβ. A, Visuospatial memory (Visual Reproduction immediate and delay recall) is associated with the interaction of MPL tau and HC-RsC FC strength. B, Verbal memory (CVLT immediate and long delay free recall) does not exhibit a significant interaction. Plots display the relationship predicted by linear regression at low (10th percentile), median, and high (90th percentile) MPL suprathreshold tau. Error bars indicate 95% confidence interval.
Tables
Mean (SD) or n (%) Range Age (years) 76.4 (6.1) 60–93 Education (years) 16.8 (1.9) 12–20 MMSE 28.6 (1.3) 25–30 Global Aβ PET 1.17 (0.25) 0.92–1.89 Sex (female) 58 (59.8) Aβ+ 43 (45.7) APOE ε4+ 28 (29.8) Demographic information for sample of 97 cognitively normal older adults including age, years of education, mini mental state examination (MMSE) score, global Aβ PET signal, sex, Aβ positivity status (Aβ+), and apolipoprotein E positivity status (APOE ε4+).
Independent variables: Dependent variable: MPL suprathreshold tau Age β = −0.002
p = 0.321Sex β = 0.007
p = 0.708Global Aβ β = 0.050
p = 0.241Choroid plexus signal β = −0.012
p = 0.208HC mean tau β = 0.263***
p < 0.001HC-RsC FC strength β = 0.123**
p = 0.005HC mean tau × HC-RsC FC strength β = 0.607**
p = 0.008Constant β = 0.066
p = 0.281Effects from linear regression model examining the relationship between medial parietal lobe (MPL) suprathreshold tau and age, sex, global Aβ, choroid plexus signal (partial volume corrected FTP SUVR), HC mean tau (partial volume corrected FTP SUVR), HC-RsC functional connectivity (FC) strength, and HC mean tau × HC-RsC FC strength interaction. Bolded term indicates interaction effect visualized in Figure 3. See Extended Data Table 2-1 for model results using FTP SUVR from EC instead of HC;
*p < 0.05,
↵**p < 0.01,
↵***p < 0.001.
Independent variables: Dependent variable: Episodic memory composite Age β = −0.048**
p = 0.005Sex β = −0.105
p = 0.540Years of education β = 0.037
p = 0.420Practice effects β = 0.253*
p = 0.019Global Aβ β = −0.308
p = 0.395MPL suprathreshold tau β = 1.130
p = 0.284HC-RsC FC strength β = 0.079
p = 0.843MPL suprathreshold tau × HC-RsC FC strength β = −9.531*
p = 0.018Constant β = 0.139
p = 0.772Effects from linear regression model examining the relationship between episodic memory performance (CVLT immediate and long-delay free recall, Visual Reproduction immediate and delay recall) and age, years of education, practice effects (see Materials and Methods), global Aβ, MPL suprathreshold tau, HC-RsC FC strength, and MPL suprathreshold tau × HC-RsC FC strength interaction. Bolded term indicates interaction effect visualized in Figure 4;
↵*p < 0.05,
↵**p < 0.01,
***p < 0.001.
Extended Data Figure 1-1
Hippocampal-superior frontal resting state functional connectivity is not associated with medial parietal lobe tau accumulation. A, SFG (medial portion of Brodmann area 10) exhibits resting state functional connectivity with HC (β = 0.40, p < 0.001) but not with pmEC (β = –0.02, p = 0.379) or alEC (β = 0.02, p = 0.439). Line color and thickness correspond to t statistic of one-sample t test of β values. B, Adjusting for age, sex, and global Aβ, HC-SFG functional connectivity strength is not associated with proportion of voxels above threshold (SUVR > 1.4) within medial parietal lobe. Connectivity strength measured by extracting β values of semipartial correlations between HC and SFG. Download Figure 1-1, TIF file.
Extended Data Figure 2-1
HC-RsC resting state functional connectivity is specifically associated with medial parietal lobe tau accumulation. A, HC-RsC is not associated with EC suprathreshold tau. B, HC-RsC shows a trend-level association with IT suprathreshold tau. C, HC-RsC is not associated with MPL Aβ measured by PiB PET DVR. Plots show residualized values from linear regression models adjusting for age, sex, and global Aβ. Connectivity strength measured by extracting β values of semipartial correlations between HC and RsC. Suprathreshold tau defined as proportion of voxels above threshold (SUVR > 1.4) within each ROI. Download Figure 2-1, TIF file.
Extended Data Table 2-1
Summary of model results with medial parietal tau as outcome. Download Table 2-1, DOCX file.
Extended Data Figure 3-1
Entorhinal tau pathology exhibits greatest association with medial parietal lobe tau when HC-RsC connectivity is greatest. Visualization of interaction between EC mean tau (partial volume corrected FTP SUVR) and HC-RsC (Extended Data Table 2-1). Medial parietal lobe (MPL) suprathreshold tau is associated with an entorhinal tau × HC-RsC interaction at trend level. Plot displays the relationship predicted by linear regression at low (10th percentile), median, and high (90th percentile) HC-RsC. Download Figure 3-1, TIF file.
