Demonstrating the usefulness of a two-stage approach in characterising the evolution of correlated cognitive and clinical outcomes

A key challenge for the secondary prevention of Alzheimer’s dementia is the need to identify individuals early on in the disease process through sensitive cognitive tests and biomarkers. The European Prevention of Alzheimer’s Dementia (EPAD) consortium recruited participants into a longitudinal cohort study with the aim of building a readiness cohort for a proof-of-concept clinical trial and also to generate a rich longitudinal data-set for disease modelling.

Data have been collected on a wide range of measurements including cognitive outcomes, neuroimaging, cerebrospinal fluid biomarkers, genetics and other clinical and environmental risk factors, and are available for 1,828 eligible participants at baseline, 1,567 at 6 months, 1,188 at one-year follow-up, 383 at 2 years, and 89 participants at three-year follow-up visit.

The researchers novelly apply state-of-the-art longitudinal modelling and risk stratification approaches to these data in order to characterise disease progression and biological heterogeneity within the cohort. Specifically, they use longitudinal class-specific mixed effects models to characterise the different clinical disease trajectories and a semi-supervised Bayesian clustering approach to explore whether participants can be stratified into homogeneous subgroups that have different patterns of cognitive functioning evolution, while also having subgroup-specific profiles in terms of baseline biomarkers and longitudinal rate of change in biomarkers.

The research leading to these results has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115736. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

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