Can we better predict and stage disease progression in dementia?
Dementia Frontiers Fund Research Question
Context
The progression of Alzheimer’s disease and related dementias differs among individuals, influenced by an interplay of genetic, molecular, and environmental factors. Although biomarker research has advanced significantly, the precise temporal cascade and mechanisms driving the transition from preclinical pathology to symptomatic stages remain poorly understood.
Challenges
Despite advances, it remains unclear which molecular and cellular events most strongly predict symptom onset or rapid decline. Current staging tools often fail to capture disease complexity, and longitudinal data linking biomarkers to clinical outcomes are limited. Predictive models lack validation, and integration across biological, behavioural, and digital data sources is still insufficient.
Opportunities & Expertise
Combining biomarkers from imaging, fluid tests, cognitive assessments, and digital tools can improve tracking of disease progression. Longitudinal studies, especially starting in preclinical stages, can reveal early disease changes. Machine learning also offers powerful tools for predicting individual trajectories.
This topic may benefit from an interdisciplinary team bringing together diverse areas of expertise ranging from molecular and cellular neuroscience, glial and synaptic biology, and longitudinal biomarker research to digital phenotyping and computational modelling. Expertise in clinical neurology, machine learning, and trial design could be particularly valuable in efforts to predict and intervene in disease progression.
Impact
More accurate staging tools and predictive models can inform decisions about when and how to intervene, both in clinical trials and in routine care. Identifying the key drivers of progression will support the development of timely, stage-appropriate interventions, increasing the likelihood of therapeutic success. This can also help to refine inclusion criteria, optimise endpoints, and enhance the interpretability of trial outcomes.
Plain English Summary
We don’t currently know when people will start to develop symptoms of dementia or how quickly those symptoms will progress. A better understanding of disease stages could lead to earlier, more accurate diagnosis and help identify people likely to decline quickly - making trials faster, cheaper, and more efficient, and speeding up the development of effective treatments.