Casamitjana, A;
Petrone, P;
Luis Molinuevo, J;
Domingo Gispert, J;
Vilaplana, V;
(2020)
Projection to Latent Spaces Disentangles Pathological Effects on Brain Morphology in the Asymptomatic Phase of Alzheimer's Disease.
Frontiers in Neurology
, 11
, Article 648. 10.3389/fneur.2020.00648.
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Abstract
Alzheimer’s disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers, such as cerebrospinal fluid (CSF) levels of Aβ, p-tau, and t-tau. In parallel, brain anatomy can be characterized through imaging techniques, such as magnetic resonance imaging (MRI). In this work we relate both sets of measurements and seek associations between biomarkers and the brain structure that can be indicative of AD progression. The goal is to uncover underlying multivariate effects of AD pathology on regional brain morphological information. For this purpose, we used the projection to latent structures (PLS) method. Using PLS, we found a low dimensional latent space that best describes the covariance between both sets of measurements on the same subjects. Possible confounder effects (age and sex) on brain morphology are included in the model and regressed out using an orthogonal PLS model. We looked for statistically significant correlations between brain morphology and CSF biomarkers that explain part of the volumetric variance at each region-of-interest (ROI). Furthermore, we used a clustering technique to discover a small set of CSF-related patterns describing the AD continuum. We applied this technique to the study of subjects in the whole AD continuum, from the pre-clinical asymptomatic stages all the way through to the symptomatic groups. Subsequent analyses involved splitting the course of the disease into diagnostic categories: cognitively unimpaired subjects (CU), mild cognitively impaired subjects (MCI), and subjects with dementia (AD-dementia), where all symptoms were due to AD.
| Type: | Article |
|---|---|
| Title: | Projection to Latent Spaces Disentangles Pathological Effects on Brain Morphology in the Asymptomatic Phase of Alzheimer's Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fneur.2020.00648 |
| Publisher version: | https://doi.org/10.3389/fneur.2020.00648 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Alzheimer’s disease, PLS, pre-clinical AD, latent model, CSF biomarkers, brain morphology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10108942 |
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