Periodic Reporting for period 3 - Brain Health Toolbox (The Brain Health Toolbox: Facilitating personalized decision-making for effective dementia prevention)
Reporting period: 2022-02-01 to 2023-07-31
Dementia and Alzheimer’s disease (AD) are a major public health challenge in the context of worldwide population aging. Brain pathology progresses gradually over a long time period before dementia onset, thus creating a window of opportunity for prevention. Early identification of at-risk individuals who are also most likely to respond to interventions is crucial. Due to the complex, multifactorial nature of dementia/AD, multimodal interventions targeting several risk factors and disease mechanisms simultaneously may also be needed for effective prevention.
The Brain Health Toolbox is designed to create a seamless continuum from accurate dementia prediction to effective prevention by i) developing disease models and prediction tools for multimodal prevention; ii) testing in actual multimodal prevention trials; and iii) bridging the gap between nonpharmacological and pharmacological interventions by designing a combined multimodal prevention trial.
The Brain Health Toolbox is designed to create a seamless continuum from accurate dementia prediction to effective prevention by i) developing disease models and prediction tools for multimodal prevention; ii) testing in actual multimodal prevention trials; and iii) bridging the gap between nonpharmacological and pharmacological interventions by designing a combined multimodal prevention trial.
1. Developing and improving disease models and prediction tools for dementia prevention. We have conducted multifactorial disease/risk prediction modelling using multiple complementary approaches: observational and interventional data (multimodal lifestyle-based trials); analysis methods ranging from machine learning to traditional statistics; outcomes ranging from cognition/dementia to specific brain pathologies; multi-dimensional predictors (e.g. cognitive, clinical, biomarkers, genetic and environmental factors; some new/less investigated biomarkers were first tested individually to assess suitability for inclusion in multi-dimensional models); target populations with broad age range (50+), covering the entire disease continuum.
2. Testing in multimodal lifestyle prevention trials. Three test scenarios have been considered: selecting target populations, assessing heterogeneity of intervention effects, and trial outcomes. Results so far have been used for the development of the first global network of multimodal lifestyle-based dementia prevention trials (World-Wide FINGERS). The results have directly contributed to the harmonized design of intervention trials in the network (e.g. aspects related to participant selection process and enrolment criteria, intervention design, outcome definitions).
3. Designing a combined prevention trial (multimodal non-pharmacological and pharmacological). With several AD drug trial failures during 2019-2020, we started with drug repurposing. A protocol has been developed for the first randomized controlled trial combining a multimodal lifestyle intervention with a repurposed putative disease-modifying drug.
Several measures have also been taken to mitigate the impact of the COVID-19 pandemic on project work.
2. Testing in multimodal lifestyle prevention trials. Three test scenarios have been considered: selecting target populations, assessing heterogeneity of intervention effects, and trial outcomes. Results so far have been used for the development of the first global network of multimodal lifestyle-based dementia prevention trials (World-Wide FINGERS). The results have directly contributed to the harmonized design of intervention trials in the network (e.g. aspects related to participant selection process and enrolment criteria, intervention design, outcome definitions).
3. Designing a combined prevention trial (multimodal non-pharmacological and pharmacological). With several AD drug trial failures during 2019-2020, we started with drug repurposing. A protocol has been developed for the first randomized controlled trial combining a multimodal lifestyle intervention with a repurposed putative disease-modifying drug.
Several measures have also been taken to mitigate the impact of the COVID-19 pandemic on project work.
Moving beyond the state of the art has included predicting early brain pathology vs cognitive trajectories in real-life interventions and clinical setting; new evidence from intervention studies on genetic-lifestyle interactions and the window of opportunity for dementia prevention; development of the first global network for multimodal dementia prevention trials; and the first multimodal precision prevention trial design combining lifestyle intervention with a repurposed putative disease-modifying drug.