%K Alzheimer’s disease, PLS, pre-clinical AD, latent model, CSF biomarkers, brain morphology
%T Projection to Latent Spaces Disentangles Pathological Effects on Brain Morphology in the Asymptomatic Phase of Alzheimer's Disease
%D 2020
%V 11
%O This
is an open-access article distributed under the terms of the Creative Commons
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%A A Casamitjana
%A P Petrone
%A J Luis Molinuevo
%A J Domingo Gispert
%A V Vilaplana
%J Frontiers in Neurology
%L discovery10108942
%I FRONTIERS MEDIA SA
%X 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.