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Project Topic
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Neurodegenerative diseases represent one of the main public health issues in our western societies and one of the
greatest challenges in drug development. Prevention policies have become essential to address these issues:
primary prevention to prevent disease onset by acting on actionable risk factors, or secondary prevention to slow
disease progression with very early therapeutic interventions, ideally at pre-symptomatic stages. Key to the
implementation of such prevention measures is the identification of at-risk patients, at the point of care, and
preferably long before disease onset.
Our project, LeMeReND, proposes to use electronic health records (EHR) to identify biomedical risk factors through
studying previous diagnoses (pre-clinical comorbidities), drug prescription, clinical care usage, and biological test
results. This analysis will use longitudinal data in EHR registries including millions of patients who have been
followed for at least 10 years before diagnosis in 4 different healthcare systems: Australia, France, the UK and
Sweden and across 4 therapeutic areas: Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies and
motor neuron diseases. We will identify the biomedical risk factors that are common to these diseases and the ones
differentiating them.
We will stratify patients based on the progression profile of their exposure to the set of risk factors, in order to
design tailored primary prevention measures. We will also design a screening tool which will give each patient a
propensity score to develop one of these neurodegenerative diseases. Such a tool could be deployed at the point of
care to prioritise at-risk individuals for further inclusion in secondary prevention trials. We will evaluate the economic
and social benefits of this new generation of precision prevention measures. We will study the public acceptability of
a secondary-prevention effort, among the French population, and the feasibility of its implementation in primary care
practices in France, Australia, and Sweden. Eventually, we will progress our understanding of the genetic and
imaging markers of the disorders by studying the identified prodromal biomedical factors, using the UK BioBank and
GWAS summary statistics. This will progress our understanding of the pathological processes which result in an
increased risk to develop a specific neurodegenerative disease.
LeMeReND gathers a multidisciplinary research group with a leading expertise in epidemiology, statistics and
machine learning, in particular for the analysis of longitudinal EHR data. Partners have demonstrated a strong track
record on neurodegenerative diseases (Sweden, France, Australia), analyses of large-scale data including
neuroimaging (France), genetics (Australia), longitudinal modelling (Sweden, France), and machine learning
(Australia, France). An expert team in health economics and health policy complements the consortium.
LeMeReND will therefore provide invaluable insights to inform health policies and highlight possible new therapeutic
targets. It will provide unique screening tools to facilitate the large-scale recruitment of patients in secondary
prevention trials.
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