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the Alzheimer's Disease Neuroimaging Initiative,

Publications and source records attributed to the Alzheimer's Disease Neuroimaging Initiative,.

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Reproducible evaluation of classification methods in Alzheimer’s disease: framework and application to MRI and PET data

A large number of papers have introduced novel machine learning and feature extraction methods for automatic classification of Alzheimers disease (AD). However, while the vast majority of these works use the public dataset ADNI for evaluation, they are difficult to reproduce because different key components of the validation are often not readily available. These components include selected participants and input data, image preprocessing and cross-validation procedures. The performance of the different approaches is also difficult to compare objectively. In particular, it is often difficult to assess which part of the method (e.g. preprocessing, feature extraction or classification algorithms) provides a real improvement, if any. In the present paper, we propose a framework for reproducible and objective classification experiments in AD using three publicly available datasets (ADNI, AIBL and OASIS). The framework comprises: i) automatic conversion of the three datasets into a standard format (BIDS); ii) a modular set of preprocessing pipelines, feature extraction and classification methods, together with an evaluation framework, that provide a baseline for benchmarking the different components. We demonstrate the use of the framework for a large-scale evaluation on 1960 participants using T1 MRI and FDG PET data. In this evaluation, we assess the influence of different modalities, preprocessing, feature types (regional or voxel-based features), classifiers, training set sizes and datasets. Performances were in line with the state-of-the-art. FDG PET outperformed T1 MRI for all classification tasks. No difference in performance was found for the use of different atlases, image smoothing, partial volume correction of FDG PET images, or feature type. Linear SVM and L2-logistic regression resulted in similar performance and both outperformed random forests. The classification performance increased along with the number of subjects used for training. Classifiers trained on ADNI generalized well to AIBL and OASIS, performing better than the classifiers trained and tested on each of these datasets independently. All the code of the framework and the experiments is publicly available.

neuroscience

Data-driven approaches improve Tau-PET biomarkers in Alzheimer’s disease

Previous positron emission tomography (PET) studies have quantified filamentous tau pathology using regions-of-interest (ROIs) based on observations of the topographical distribution of neurofibrillary tangles in post-mortem tissue. However, such approaches may not take full advantage of information contained in neuroimaging data. The present study employs an unsupervised data-driven method to identify spatial patterns of tau-PET distribution, and to compare these patterns to previously published \"pathology-driven\" ROIs. Tau-PET patterns were identified from a discovery sample comprised of 123 normal controls and patients with mild cognitive impairment or Alzheimers disease (AD) dementia from the Swedish BioFINDER cohort, who underwent [18F]AV1451 PET scanning. Associations with cognition were tested in a separate sample of 90 individuals from ADNI. BioFINDER [18F]AV1451 images were entered into a robust voxelwise stable clustering algorithm, which resulted in five clusters. Mean [18F]AV1451 uptake in the data-driven clusters, and in 35 previously published pathology-driven ROIs, was extracted from ADNI [18F]AV1451 scans. We performed linear models comparing [18F]AV1451 signal across all 40 ROIs to several tests of global cognition, adjusting for age, sex and education. Two data-driven ROIs consistently demonstrated the strongest or near-strongest effect sizes across all cognitive tests. Inputting all regions plus demographics into a feature selection routine resulted in selection of two ROIs (one data-driven, one pathology-driven) and education, which together explained 28% of the variance of a global cognitive composite score. Our findings suggest that [18F]AV1451-PET data naturally clusters into spatial patterns that are biologically meaningful and that may offer advantages as clinical tools.

neuroscience

Multivariate genotypic analyses that identify specific genotypes to characterize disease and control groups in ADNI

INTRODUCTIONGenetic contributions to Alzheimers Disease (AD) are likely polygenic and not necessarily explained by uniformly applied linear and additive effects. In order to better understand the genetics of AD, we require statistical techniques to address both polygenic and possible non-additive effects.\n\nMETHODSWe used partial least squares-correspondence analysis (PLS-CA)--a method designed to detect multivariate genotypic effects. We used ADNI-1 (N = 756) as a discovery sample with two forms of PLS-CA: diagnosis-based and ApoE-based. We used ADNI-2 (N= 791) as a validation sample with a diagnosis-based PLS-CA.\n\nRESULTSWith PLS-CA we identified some expected genotypic effects (e.g., APOE/TOMM40, and APP) and a number of new effects that include, for examples, risk-associated genotypes in RBFOX1 and GPC6 and control-associated genotypes in PTPN14 and CPNE5.\n\nDISCUSSIONThrough the use of PLS-CA, we were able to detect complex (multivariate, genotypic) genetic contributions to AD, which included many non-additive and non-linear risk and possibly protective effects.

genomics