Catalyst Awardee

Project Description

Investigating Associations Between Biological Age measured by Blood-Based DNA Methylation, with Cognitive Performance, Neuroimaging Markers and Conversion to Dementia – A Nested Case Control Longitudinal Study

Dr Ming Ann Sim | National University Hospital (NUH); A/Prof Christopher Chen | NUS; Prof Andrea Britta Maier | NUS; Prof Roger Foo Sik Yin | IMCB; Dr Rajkumar s/o Dorajoo | GIS
Competition Sponsor: Ministry of Health and National Research Foundation of Singapore
Awardee year: 2023

This proof-of-concept study will leverage upon an existing memory clinic cohort, with longitudinal data collected. 360 patients stratified into 3 groups for inclusion: 60 dementia converters, 150 cognitively normal controls, 150 with baseline dementia.
The primary outcomes are 1) Cross-sectional cognitive performance, 2) Neuroimaging markers, and 3) Longitudinal conversion to dementia with 4) Stratification for dementia causative subtype.
High-throughput measurement of DNA methylation on a genome wide scale will be performed. Four machine-learning derived blood-DNA methylation aging clocks will be calculated. Differences in DNA methylation clocks will be evaluated on cross-sectional and longitudinal analysis of cognitive outcomes. The incremental predictive value of DNA methylation clocks will be compared with existing circulating biomarkers for dementia. Differentially methylation region analysis and gene pathway analysis will be employed to identify significant differences in methylation profile with regards to neurocognitive outcomes of interest.
Taken together, this study will 1) Investigate biomarkers of biological age which may add predictive value to current markers for dementia, 2) Uncover mechanistic insights between the epigenome and dementia pathophysiology; and 3) Identify potential therapeutic targets for dementia.

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