TACKLing the challenges of PREsymptomatic sporadic Dementia

Alzheimer’s disease and other dementias are becoming an epidemic and there is a great need to develop therapies to prevent or delay onset. However, clinical trials to date have failed to find effective drugs. One reason for these failures may be multiple underlying co-pathologies in participants. In fact, mixed pathology is extremely common in late-onset sporadic dementia.

Thus, drugs targeting a single neuropathological entity may not be sufficient to induce a detectable clinical change.The project aim is to identify how genomic/age/education/sex/cardiovascular risk factors, together with serum/plasma protein biomarkers, impact neuroimaging and cognitive/behavioural phenotypes across neurodegenerative diseases.

Based on this data dementia biotypes (pure vs mixed) will be defined. The dementia biotypes will be validated in an autopsy-confirmed subset.

Furthermore, a longitudinal ageing study will be used to evaluate how well the dementia biotypes determine risk for dementia and whether they predict mixed or pure forms.

Methodologies include genomic screening, fluid biomarker analysis and multimodal analysis of biological variables and risk factors.

By understanding the mechanisms leading to the underlying pathological complexity in late-onset sporadic dementia, a critical knowledge gap will be closed, and results may have an impact on future clinical trial design, including patient selection.