Machine learning for brain age prediction: Introduction to methods and clinical applications.

The rise of machine learning has unlocked new ways of analysing structural neuroimaging data, including brain age prediction. In this state-of-the-art review, we provide an introduction to the methods and potential clinical applications of brain age prediction. Studies on brain age typically involve the creation of a regression machine learning model of age-related neuroanatomical changes in healthy people. This model is then applied to new subjects to predict their brain age. The difference between predicted brain age and chronological age in a given individual is known as 'brain-age gap'. This value is thought to reflect neuroanatomical abnormalities and may be a marker of overall brain health. It may aid early detection of brain-based disorders and support differential diagnosis, prognosis, and treatment choices. These applications could lead to more timely and more targeted interventions in age-related disorders.

Using normative modelling to detect disease progression in mild cognitive impairment and Alzheimer's disease in a cross-sectional multi-cohort study.

Normative modelling is an emerging method for quantifying how individuals deviate from the healthy populational pattern. Several machine learning models have been implemented to develop normative models to investigate brain disorders, including regression, support vector machines and Gaussian process models. With the advance of deep learning technology, the use of deep neural networks has also been proposed. In this study, we assessed normative models based on deep autoencoders using structural neuroimaging data from patients with Alzheimer's disease (n = 206) and mild cognitive impairment (n = 354). We first trained the autoencoder on an independent dataset (UK Biobank dataset) with 11,034 healthy controls. Then, we estimated how each patient deviated from this norm and established which brain regions were associated to this deviation. Finally, we compared the performance of our normative model against traditional classifiers. As expected, we found that patients exhibited deviations according to the severity of their clinical condition. The model identified medial temporal regions, including the hippocampus, and the ventricular system as critical regions for the calculation of the deviation score. Overall, the normative model had comparable cross-cohort generalizability to traditional classifiers. To promote open science, we are making all scripts and the trained models available to the wider research community.

Brain age prediction: A comparison between machine learning models using region- and voxel-based morphometric data.

Brain morphology varies across the ageing trajectory and the prediction of a person's age using brain features can aid the detection of abnormalities in the ageing process. Existing studies on such "brain age prediction" vary widely in terms of their methods and type of data, so at present the most accurate and generalisable methodological approach is unclear. Therefore, we used the UK Biobank data set (N = 10,824, age range 47-73) to compare the performance of the machine learning models support vector regression, relevance vector regression and Gaussian process regression on whole-brain region-based or voxel-based structural magnetic resonance imaging data with or without dimensionality reduction through principal component analysis. Performance was assessed in the validation set through cross-validation as well as an independent test set. The models achieved mean absolute errors between 3.7 and 4.7 years, with those trained on voxel-level data with principal component analysis performing best. Overall, we observed little difference in performance between models trained on the same data type, indicating that the type of input data had greater impact on performance than model choice. All code is provided online in the hope that this will aid future research.