Projects per year
Abstract
Results from large cohort studies investigating the association between inflammation and cognition have been mixed, possibly due to methodological disparities. However, a key issue in research utilising inflammatory biomarkers is their typically phasic responses. C-reactive protein (CRP) is widely used to investigate the association between chronic inflammation and cognition, but its plasma concentrations can markedly deviate in response to acute infection. Recently a large-scale epigenome-wide association study identified DNA methylation correlates of CRP. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. Here, we generate an epigenetic CRP score and investigate its trajectories with age, and associations with cognitive ability, in comparison to serum CRP in two cohorts: a longitudinal study of older adults (the Lothian Birth Cohort 1936, n=889) and a large, cross-sectional cohort (Generation Scotland, n=7,028).
We identified differing trajectories of serum CRP across the cohorts, with no homogeneous trends seen with age. Conversely, the epigenetic score was consistently found to increase with age, and to do so more rapidly in males compared to females. Higher levels of serum CRP were found to associate with poorer cognition in Lothian Birth Cohort 1936, but not in Generation Scotland. However, a consistent negative association was identified between cognition and the epigenetic score in both cohorts. Furthermore, the epigenetic score accounted for a greater proportion of variance in cognitive ability.
Our results suggest that epigenetic signatures of acute inflammatory markers may provide an enhanced signature of chronic inflammation, allowing for more reliable stratification of individuals, and thus clearer inference of associations with incident health outcomes.
We identified differing trajectories of serum CRP across the cohorts, with no homogeneous trends seen with age. Conversely, the epigenetic score was consistently found to increase with age, and to do so more rapidly in males compared to females. Higher levels of serum CRP were found to associate with poorer cognition in Lothian Birth Cohort 1936, but not in Generation Scotland. However, a consistent negative association was identified between cognition and the epigenetic score in both cohorts. Furthermore, the epigenetic score accounted for a greater proportion of variance in cognitive ability.
Our results suggest that epigenetic signatures of acute inflammatory markers may provide an enhanced signature of chronic inflammation, allowing for more reliable stratification of individuals, and thus clearer inference of associations with incident health outcomes.
Original language | English |
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Article number | 113 |
Journal | Clinical Epigenetics |
Volume | 12 |
DOIs | |
Publication status | Published - 27 Jul 2020 |
Keywords
- epigenetics
- DNA methylation
- C-reactive protein
- inflammation
- cognitive ability
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RA2662 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Porteous, D.
1/09/13 → 31/08/19
Project: Research
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Generation Scotland
Porteous, D.
UK central government bodies/local authorities, health and hospital authorities
1/04/11 → 31/03/14
Project: Research
Research output
- 1 Doctoral Thesis
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A multi–omics approach to understand the role of plasma proteins in cognitive ageing and dementia
Hillary, R., 2021Research output: Thesis › Doctoral Thesis
Profiles
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Andrew McIntosh
- Deanery of Clinical Sciences - Chair of Biological Psychiatry
- Centre for Clinical Brain Sciences
- Edinburgh Neuroscience
- Edinburgh Imaging
Person: Academic: Research Active