There is now consensus that neurodegenerative disease, including Alzheimer’s disease (AD), starts in mid-life and manifests in later life as dementia and related disorders, but the understanding of early disease mechanisms is lacking. The PREVENT dementia programme is the world’s largest study investigating the origins and early diagnosis of dementia in a mid-life “at risk” cohort. It has recruited and deeply phenotyped 700 participants aged 40-59, across five centres in the UK, and at Trinity College Dublin, in Ireland. Core assessments include cognitive testing, neuropsychiatric evaluation, genetics, lifestyle risk factor analysis, and multi-modal MRI imaging, with samples of blood, urine, saliva and CSF collected. The programme has undertaken recruitment, with wave 2 (3 year) follow-up in all sites with excellent retention, and wave 3 (7 year) follow-up ongoing in the UK sites. This application seeks funding to carry out wave 3 at Trinity College Dublin.
Our findings have already had great impact, identifying early cognitive, vascular, metabolic, and structural changes that develop 20 years before disease onset, and providing key evidence defining the optimal age to target early therapeutics. This unique dataset at 3 waves, as participants approach symptomatic stages, will address key mechanistic and diagnostic questions, including the relationship between progressive vascular, metabolic, and brain functional and structural changes as the disease develops.
This pathophysiological mechanistic understanding will be critical for identifying (a) novel, early and sensitive biomarkers, (b) tractable mechanisms for targeting therapeutics and designing clinical trials, and (c) how and when to optimally apply new diagnostic tools and biomarkers for early dementia detection. The project will significantly enhance Ireland’s competitiveness in knowledge generation, human capacity, health and wellbeing, professional services, and international engagement.