Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - EuroPOND (Data-driven models for Progression Of Neurological Disease)

Teaser

EuroPOND is developing uniquely powerful data-driven statistical-and-computational models of neurological disease progression. The models are fundamentally new avenues for understanding the complexity of clinical phenotypes in multifactorial neurological diseases. We...

Summary

EuroPOND is developing uniquely powerful data-driven statistical-and-computational models of neurological disease progression. The models are fundamentally new avenues for understanding the complexity of clinical phenotypes in multifactorial neurological diseases. We demonstrate the models by eliciting new knowledge in a variety of neurological applications. The models offer innovation potential by underpinning support systems for clinical and drug-development applications. Specifically, they enable “Precision Medicine” by providing differential and personalised diagnosis, fine-grained staging, and personalised prognosis. These advances will position Europe as world leaders in one of the biggest challenges facing 21st century healthcare: management of neurological disease.
Our specific objectives are:
A. Develop, and implement as a prototype software tool, a new data-driven computational-and- statistical modelling framework for disease progression.
B. Construct a quantitative validation framework using well-phenotyped and other complementary data sets from across the European arena.
C. Construct models for a range of neurological conditions, specifically dementia, multiple sclerosis, prion diseases, and normal and abnormal neurodevelopment and ageing.
D. Prototype a computer-assisted diagnosis and staging software system for dementia and demonstrate in relevant environments.

Work performed

The key areas of work performed during the first reporting period were:
• Collation of a range of imaging-plus-X data sets in each neurological application (WP2).
• Agreement across the consortium of the set of relevant computational methods and initial best practice guidelines for their usage (WP2).
• Development of a suite of new computational disease-progression modelling tools including the Subtype and Stage Inference algorithm, the Discriminative Event-Based Model, various refined Scalar Trajectory Models within a Bayesian framework, and new Bayesian Spatio-temporal models (WP3).
• Design of a simulation framework for enhanced development and validation of models (WP3).
• Prototype of a unified modelling framework for neurological disease progression (WP3).
• Development of an early prototype system for clinical usage exploiting the event-based model in dementia (WP4).
• Exploration of generalizability of event-based models among data sets distinct from their training data (WP5).
• Construction of progression models of normal ageing for comparison with disease progression models (WP6).
• First models of disease progression in multiple sclerosis combining markers from imaging and neuropsychological assessments (WP7).
• First models of disease progression in prion disease, mainly based on imaging (MRI) (WP8).
• First explorations of longitudinal effects in early neurodevelopment primarily using MRI (WP9).
• An informative project video, in multiple versions (short/medium/full duration), available for free to the public via YouTube.
• POND2016 international workshop in London, UK.


During the second reporting period we advanced this knowledge through new methods development (WP3) and new application across diseases. Key outputs include:
• Delivery of a unified, open-source software toolbox for neurological disease progression modelling (WP3).
• Enhancement of models including improved computational efficiency, handling missing data and correlated variables, shape modelling, and nonparametric mixture modelling (WP3).
• Development and demonstration of the first subtype models able to disentangle phenotypic variation from temporal change and demonstration in Alzheimer’s disease (WP3).
• Extensive evaluation of our model enhancements from the first reporting period (WP3).
• Iteration of our clinical prototype tool, both in the back-end and front-end (WP4).
• Advanced models of dementia, including new knowledge on the effects of fixed variables (WP5 and WP3).
• Basic models of population ageing (WP6).
• New models (DEBM) of multiple sclerosis progression (WP7).
• Advanced understanding of variability in prion disease mechanisms (WP8).
• Ongoing organization of the internationally-acclaimed TADPOLE Challenge for predicting Alzheimer’s disease, including live webinars.
• POND2018 international workshop in Geneva, Switzerland.

Final results

Primary developments beyond the state of the art so far are in novel computational modelling technology, although these are already providing new insight into disease aetiology and progression that has extended state-of-the-art understanding.

Management and treatment of neurological diseases is one of the biggest challenges facing medicine today:
• Annual socioeconomic costs of Alzheimer\'s disease alone in the EU (around 5M patients) exceed €200B; other dementias combined have a similar cost. The costs will rise rapidly with the ageing population.
• Prion diseases are rare, but devastating, with an incidence of about 2 cases per million per year (rising to 5 per million for over 60s), and life expectancy is less than one year (NHS2014).
• Multiple sclerosis affects over 2M people worldwide, with around two-thirds being female, and onset is often early (20–35 years of age). Prevalence is highest in the USA and Europe, where up to 1400 people per million are affected (MSIF2013).
• Neurocognitive disorders touch 27% of the European population; 5% of children suffer from attention deficit hyperactivity disorders and autism; childhood and adult depression are increasing. The disorders are increasingly associated with prematurity or low birth weight.

The impact of EuroPOND\'s work is to facilitate therapy development and deployment through earlier and discriminative diagnosis, as well as clear and consistent staging and stratification.

Website & more info

More info: http://europond.eu.