Patients with Mild Cognitive Impairment (MCI) have an increased risk of Alzheimer’s disease (AD). Early identification of underlying neurodegenerative processes is essential to provide treatment before the disease is well established in the brain. Here we used longitudinal data from the ADNI database to investigate prediction of a trajectory towards AD in a group of patients defined as MCI at a baseline examination. One group remained stable over time (sMCI, n = 357) and one converted to AD (cAD, n = 321). By running two independent classification methods within a machine learning framework, with cognitive function, hippocampal volume and genetic APOE status as features, we obtained a cross-validation classification accuracy of about 70%. This level of accuracy was confirmed across different classification methods and validation procedures. Moreover, the sets of misclassified subjects had a large overlap between the two models. Impaired memory function was consistently found to be one of the core symptoms of MCI patients on a trajectory towards AD. The prediction above chance level shown in the present study should inspire further work to develop tools that can aid clinicians in making prognostic decisions.

Patients with Mild Cognitive Impairment (MCI) have an increased risk of Alzheimer’s disease (AD). Early identification of underlying neurodegenerative processes is essential to provide treatment before the disease is well established in the brain. Here we used longitudinal data from the ADNI database to investigate prediction of a trajectory towards AD in a group of patients defined as MCI at a baseline examination. One group remained stable over time (sMCI, n = 357) and one converted to AD (cAD, n = 321). By running two independent classification methods within a machine learning framework, with cognitive function, hippocampal volume and genetic APOE status as features, we obtained a cross-validation classification accuracy of about 70%. This level of accuracy was confirmed across different classification methods and validation procedures. Moreover, the sets of misclassified subjects had a large overlap between the two models. Impaired memory function was found to be a core symptom in MCI patients on a trajectory towards AD. The prediction above chance level shown in the present study should inspire further work to develop tools that can aid clinicians in making prognostic decisions.

The present work presents a statistically sound, rigorous, and model-free algorithm – the Ledley-Jaynes machine – for use in personalized medicine. The Ledley-Jaynes machine is designed first to learn from a dataset of clinical with relevant predictors and predictands, and then to assist a clinician in the assessment of prognosis & treatment for new patients. It allows the clinician to input, for each new patient, additional patient-dependent clinical information, as well as patient-dependent information about benefits and drawbacks of available treatments. We apply the algorithm in a realistic setting for clinical decision-making, incorporating clinical, environmental, imaging, and genetic data, using a data set of subjects suffering from mild cognitive impairment and Alzheimer’s Disease. We show how the algorithm is theoretically optimal, and discuss some of its major advantages for decision-making under risk, resource planning, imputation of missing values, assessing the prognostic importance of each predictor, and more.

Background Loss of autonomy in day-to-day functioning is one of the feared outcomes of Alzheimer’s disease (AD), and relatives may have been worried by subtle behavioral changes in ordinary life situations long before these changes are given medical attention. In the present study, we ask if such subtle changes should be given weight as an early predictor of a future AD diagnosis. Methods Longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were used to define a group of adults with a mild cognitive impairment (MCI) diagnosis remaining stable across several visits (sMCI, n=360; 55-91 years at baseline), and a group of adults who over time converted from having an MCI diagnosis to an AD diagnosis (cAD, n=320; 55-88 years at baseline). Eleven features were used as input in a Random Forest (RF) binary classifier (sMCI vs. cAD) model. This model was tested on an unseen holdout part of the dataset, and further explored by three different permutation-driven importance estimates and a comprehensive post hoc machine learning exploration. Results The results consistently showed that measures of daily life functioning, verbal memory function, and a volume measure of hippocampus were the most important predictors of conversion from an MCI to an AD diagnosis. Results from the RF classification model showed a prediction accuracy of around 70% in the test set. Importantly, the post hoc analyses showed that even subtle changes in everyday functioning noticed by a close informant put MCI patients at increased risk for being on a path toward the major cognitive impairment of an AD diagnosis. Conclusion The results showed that even subtle changes in everyday functioning should be noticed when reported by relatives in a clinical evaluation of patients with MCI. Information of these changes should also be included in future longitudinal studies to investigate different pathways from normal cognitive aging to the cognitive decline characterizing different stages of AD and other neurodegenerative disorders.