Abstract

BackgroundPredicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion.MethodsIn the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question “Will a MCI patient convert to dementia somewhere in the future” to the question “Will a MCI patient convert to dementia in a specific time window”.ResultsThe proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set.ConclusionsPrognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.

Highlights

  • Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research

  • We proposed a new approach to create learning examples based on time windows, which consists in stratifying the cohort of Mild Cognitive Impairment (MCI) patients based on their conversion time, or the time that they remained MCI

  • We proposed a supervised learning approach to predict conversion of MCI to dementia based on time windows, following an innovative strategy to build the learning examples and compared it with the commonly used strategy (FL approach)

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Summary

Introduction

Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. Cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. By the time patients meet criteria for dementia, the brain has suffered sufficient damage to severely impact cognition and autonomy. With this in mind, recognizing putative progress to dementia when patients experience only mild cognitive deficits, at a stage of Mild Cognitive Impairment (MCI), is paramount to develop diseasemodifying therapies and identifying appropriate therapeutic windows [3,4,5,6,7,8,9]. In a recent systematic review [12], MCI diagnosis was associated with an annual conversion rate up to 20%, with substantial variation in risk estimates

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