Federated Morphometry Feature Selection for Hippocampal Morphometry Associated Beta-Amyloid and Tau Pathology

Abstract

Amyloid-β (Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. One of the particular neurodegenerative regions is the hippocampus to which the influence of Aβ/tau on has been one of the research focuses in the AD pathophysiological progress. This work proposes a novel framework, Federated Morphometry Feature Selection (FMFS) model, to examine subtle aspects of hippocampal morphometry that are associated with Aβ/tau burden in the brain, measured using positron emission tomography (PET). FMFS is comprised of hippocampal surface-based feature calculation, patch-based feature selection, federated group LASSO regression, federated screening rule-based stability selection, and region of interest (ROI) identification. FMFS was tested on two Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts to understand hippocampal alterations that relate to Aβ/tau depositions. Each cohort included pairs of MRI and PET for AD, mild cognitive impairment (MCI), and cognitively unimpaired (CU) subjects. Experimental results demonstrated that FMFS achieves an 89× speedup compared to other published state-of-the-art methods under five independent hypothetical institutions. In addition, the subiculum and cornu ammonis 1 (CA1 subfield) were identified as hippocampal subregions where atrophy is strongly associated with abnormal Aβ/tau. As potential biomarkers for Aβ/tau pathology, the features from the identified ROIs had greater power for predicting cognitive assessment and for survival analysis than five other imaging biomarkers. All the results indicate that FMFS is an efficient and effective tool to reveal associations between Aβ/tau burden and hippocampal morphometry.

Improved Prediction of Amyloid-β and Tau Burden Using Hippocampal Surface Multivariate Morphometry Statistics and Sparse Coding

“…This reduces the effect's interpretability to some extent, although statistically significant regions can still be shown, similar to our earlier group difference research [69,92]. However, in our recent work [93], we use group lasso screening to choose the most significant features first, and then randomly select patches to form the initial dictionary. As a result, the surface map can be used to show the features employed in sparse coding.…”

Integrating Transcriptomics, Genomics, and Imaging in Alzheimer's Disease: A Federated Model

“…Surface-based morphometry analyses have achieved excellent performance for early AD detection (66)(67)(68). In recent work (69,70), the authors created tools to generate a univariate morphometry index (UMI) for surface morphometry features on regions of interest (ROIs) that are related to beta-amyloid deposition. This induced UMI may reflect intrinsic morphological changes induced by processes of amyloid accumulation in AD and has greater signal-to-noise ratio and strong generalizability to new subjects.…”

Genetic architecture of hippocampus subfields volumes in Alzheimer’s disease

“… 2 For example, cell loss and neuropathologic changes (including intraneuronal neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein, deposition of Aβ protein, and extensive neurodegeneration) are first found in some brain regions with asymmetric and progressive atrophy, like the dorsal raphe nucleus (DRN) in the brainstem, 3 and medial temporal lobes(MTL). 4 , 5 , 6 , 7 , 8 The atrophy is believed to be associated with functional deficits in AD. 9 Hippocampal atrophy, determined by magnetic resonance imaging (MRI), 10 is considered as one of the most validated, easily accessible biomarker of AD and has been widely used.…”

“…Previous studies have shown that the hippocampus is particularly vulnerable to pathological conditions 2 . For example, cell loss and neuropathologic changes (including intraneuronal neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein, deposition of Aβ protein, and extensive neurodegeneration) are first found in some brain regions with asymmetric and progressive atrophy, like the dorsal raphe nucleus (DRN) in the brainstem, 3 and medial temporal lobes(MTL) 4–8 . The atrophy is believed to be associated with functional deficits in AD 9 .…”