Nonlinear interaction between APOE ε4 allele load and age in the hippocampal surface of cognitively intact individuals.

The ε4 allele of the gene Apolipoprotein E is the major genetic risk factor for Alzheimer's Disease. APOE ε4 has been associated with changes in brain structure in cognitively impaired and unimpaired subjects, including atrophy of the hippocampus, which is one of the brain structures that is early affected by AD. In this work we analyzed the impact of APOE ε4 gene dose and its association with age, on hippocampal shape assessed with multivariate surface analysis, in a ε4-enriched cohort of n = 479 cognitively healthy individuals. Furthermore, we sought to replicate our findings on an independent dataset of n = 969 individuals covering the entire AD spectrum. We segmented the hippocampus of the subjects with a multi-atlas-based approach, obtaining high-dimensional meshes that can be analyzed in a multivariate way. We analyzed the effects of different factors including APOE, sex, and age (in both cohorts) as well as clinical diagnosis on the local 3D hippocampal surface changes. We found specific regions on the hippocampal surface where the effect is modulated by significant APOE ε4 linear and quadratic interactions with age. We compared between APOE and diagnosis effects from both cohorts, finding similarities between APOE ε4 and AD effects on specific regions, and suggesting that age may modulate the effect of APOE ε4 and AD in a similar way.

A survey on machine and statistical learning for longitudinal analysis of neuroimaging data in Alzheimer's disease.

BACKGROUND AND OBJECTIVES: Recently, longitudinal studies of Alzheimer's disease have gathered a substantial amount of neuroimaging data. New methods are needed to successfully leverage and distill meaningful information on the progression of the disease from the deluge of available data. Machine learning has been used successfully for many different tasks, including neuroimaging related problems. In this paper, we review recent statistical and machine learning applications in Alzheimer's disease using longitudinal neuroimaging. METHODS: We search for papers using longitudinal imaging data, focused on Alzheimer's Disease and published between 2007 and 2019 on four different search engines. RESULTS: After the search, we obtain 104 relevant papers. We analyze their approach to typical challenges in longitudinal data analysis, such as missing data and variability in the number and extent of acquisitions. CONCLUSIONS: Reviewed works show that machine learning methods using longitudinal data have potential for disease progression modelling and computer-aided diagnosis. We compare results and models, and propose future research directions in the field.