Predicting the Progression of Mild Cognitive Impairment Using Machine Learning: A Systematic and Quantitative Review
2019
Context. Automatically predicting if a subject with Mild Cognitive Impairment (MCI) is going to progress to Alzheimer's disease (AD) dementia in the coming years is a relevant question regarding clinical practice and trial inclusion alike. A large number of articles have been published, with a wide range of algorithms, input variables, data sets and experimental designs. It is unclear which of these factors are determinant for the prediction, and affect the predictive performance that can be expected in clinical practice. We performed a systematic review of studies focusing on the automatic prediction of the progression of MCI to AD dementia. We systematically and statistically studied the influence of different factors on predictive performance. Method. The review included 172 articles, 93 of which were published after 2014. 234 experiments were extracted from these articles. For each of them, we reported the used data set, the feature types (defining 10 categories), the algorithm type (defining 12 categories), performance and potential methodological issues. The impact of the features and algorithm on the performance was evaluated using t-tests on the coefficients of mixed effect linear regressions. Results. We found that using cognitive, fluorodeoxyglucose-positron emission tomog-raphy or potentially electroencephalography and magnetoencephalography variables significantly improves predictive performance compared to not including them (p=0.046, 0.009 and 0.003 respectively), whereas including T1 magnetic resonance imaging, amyloid positron emission tomography or cerebrospinal fluid AD biomarkers does not show a significant effect. On the other hand, the algorithm used in the method does not have a significant impact on performance. We identified several methodological issues. Major issues, found in 23.5% of studies, include the absence of a test set, or its use for feature selection or parameter tuning. Other issues, found in 15.0% of studies, pertain to the usability of the method in clinical practice. We also highlight that short-term predictions are likely not to be better than predicting that subjects stay stable over time. Finally, we highlight possible biases in publications that tend not to publish methods with poor performance on large data sets, which may be censored as negative results. Conclusion. Using machine learning to predict MCI to AD dementia progression is a promising and dynamic field. Among the most predictive modalities, cognitive scores are the cheapest and less invasive, as compared to imaging. The good performance they offer question the wide use of imaging for predicting diagnosis evolution, and call for further exploring fine cognitive assessments. Issues identified in the studies highlight the importance of establishing good practices and guidelines for the use of machine learning as a decision support system in clinical practice.
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