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. 2023;93(3):1153-1168.
doi: 10.3233/JAD-230034.

A Surface-Based Federated Chow Test Model for Integrating APOE Status, Tau Deposition Measure, and Hippocampal Surface Morphometry

Jianfeng Wu  1 , Yi Su  2 , Yanxi Chen  1 , Wenhui Zhu  1 , Eric M Reiman  2 , Richard J Caselli  3 , Kewei Chen  2 , Paul M Thompson  4 , Junwen Wang  5 , Yalin Wang  1 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

A Surface-Based Federated Chow Test Model for Integrating APOE Status, Tau Deposition Measure, and Hippocampal Surface Morphometry

Jianfeng Wu et al. J Alzheimers Dis. 2023.

Abstract

Background: Alzheimer's disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofibrillary tangles are the primary driver of downstream neurodegeneration and subsequent cognitive impairment in AD, resulting in structural deformations such as hippocampal atrophy that can be observed in magnetic resonance imaging (MRI) scans.

Objective: To build a surface-based model to 1) detect differences between APOE subgroups in patterns of tau deposition and hippocampal atrophy, and 2) use the extracted surface-based features to predict cognitive decline.

Methods: Using data obtained from different institutions, we develop a surface-based federated Chow test model to study the synergistic effects of APOE, a previously reported significant risk factor of AD, and tau on hippocampal surface morphometry.

Results: We illustrate that the APOE-specific morphometry features correlate with AD progression and better predict future AD conversion than other MRI biomarkers. For example, a strong association between atrophy and abnormal tau was identified in hippocampal subregion cornu ammonis 1 (CA1 subfield) and subiculum in e4 homozygote cohort.

Conclusion: Our model allows for identifying MRI biomarkers for AD and cognitive decline prediction and may uncover a corner of the neural mechanism of the influence of APOE and tau deposition on hippocampal morphology.

Keywords: APOE; Alzheimer’s disease; Federated Chow test; hippocampal morphometry; tau deposition.

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Conflict of interest statement

CONFLICT OF INTEREST

Yalin Wang and Richard J. Caselli are both members of the Editorial Board of this journal but were not involved in the peer-review process nor had access to any information regarding its peer-review. The remaining authors have no conflict of interest to report.

Figures

Figure 1.
Figure 1.. An overview of our multimodal approach.
The correlations in subgroups with genotypes AA and BB remained strong after stratification but were dilated in the mixed population.
Figure 2.
Figure 2.. Our Chow test framework.
Predictors: imaging biomarkers; responses: the measure of tau. The sample cohort was stratified based on the APOE genotype.
Figure 3.
Figure 3.. System pipeline.
Subfigures (a-d) show the steps for morphometric feature extraction. After segmentation and registration from the raw MRI scan images, we generate the smoothed hippocampal surface and perform fluid registration. RD and mTBM features are calculated at each vertex. Then, subfigure (e) represents the federated Chow test model performed on each vertex feature across these institutions. Once the p-values for all the vertices are calculated, they are further visualized on the hippocampal surface, as shown in subfigure (f).
Figure 4.
Figure 4.. Correlation of hippocampal volume and a) Braak1 b) Braak34 c) Braak56 in subpopulations stratified by the sample's APOE genotype.
In each subfigure, the top four subfigures are the distributions for left hippocampal volume and regional uptake of Braak ROIs, and the bottom four are for right hippocampus and regional uptakes of Braak ROIs. The first column shows the result for all the 847 subjects and the rest for the NC, HM and HT cohorts, respectively. R and p are Pearson correlation coefficient and p-value, respectively.
Figure 5.
Figure 5.. The p-maps of our surface-based federated Chow test model results.
The warmer color regions have more significant p-values. a) Braak1; b) Braak34; c) Braak56. In each subfigure, the top two subfigures are the results for RD and the bottom two are for TBM. Braak1 results are less significantly related to tau measures under APOE-based stratification. The directionality information can be found in Figure 4.
Figure 6.
Figure 6.. Cumulative distribution functions of the p-values.
Figure 7.
Figure 7.. The ROC analysis results for hippocampal surface area, volume, the whole hippocampal feature, and the features on ROIs where Braak34 are associated with RD and TBM. The AUC for each measurement is shown in parentheses.
Figure 8.
Figure 8.. The survival probability analysis for progression to AD in MCI patients based on hippocampal surface area, volume, the whole hippocampal features, and the features on ROIs related to Braak34.
The p-values are from the log-rank test. The red curve represents the high-value (HV) group for each measurement. And the blue one represents the low-value (LV) group.
See this image and copyright information in PMC

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