Machine learning for the life-time risk prediction of Alzheimer's disease: a systematic review

Alzheimer's disease is a neurodegenerative disorder and the most common form of dementia. Early diagnosis may assist interventions to delay onset and reduce the progression rate of the disease. We systematically reviewed the use of machine learning algorithms for predicting Alzheimer's disease using single nucleotide polymorphisms and instances where these were combined with other types of data. We evaluated the ability of machine learning models to distinguish between controls and cases, while also assessing their implementation and potential biases. Articles published between December 2009 and June 2020 were collected using Scopus, PubMed and Google Scholar. These were systematically screened for inclusion leading to a final set of 12 publications. Eighty-five per cent of the included studies used the Alzheimer's Disease Neuroimaging Initiative dataset. In studies which reported area under the curve, discrimination varied (0.49-0.97). However, more than half of the included manuscripts used other forms of measurement, such as accuracy, sensitivity and specificity. Model calibration statistics were also found to be reported inconsistently across all studies. The most frequent limitation in the assessed studies was sample size, with the total number of participants often numbering less than a thousand, whilst the number of predictors usually ran into the many thousands. In addition, key steps in model implementation and validation were often not performed or unreported, making it difficult to assess the capability of machine learning models. This review assessed the literature regarding the performance of machine learning for the prediction of Alzheimer's disease using genetics. Publications were screened systematically, with 12 studies passing all criteria. Common issues such as the overreliance on one data source, insufficient sample sizes and inconsistent model performance reporting methods were outlined.