scholarly journals Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

2019 ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Robert F. Hillary ◽  
Archie Campbell ◽  
Stewart W. Morris ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Ability ◽  
Chronic Inflammation ◽  
Birth Cohort ◽  
Large Scale ◽  
Acute Infection ◽  
Plasma Concentrations ◽  
Generation Scotland ◽  
Lothian Birth Cohort ◽  
Serum Crp

ABSTRACTResults 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.

scholarly journals Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6

2021 ◽  
Author(s):  
Anna J Stevenson ◽  
Danni A Gadd ◽  
Robert F Hillary ◽  
Daniel L McCartney ◽  
Archie Campbell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Functioning ◽  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Inverse Association ◽  
Generation Scotland ◽  
Independent Test ◽  
Lothian Birth Cohort ◽  
Weighted Score ◽  
The Relationship

Abstract Background Studies evaluating the relationship between chronic inflammation and cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals’ persisting levels of inflammation. DNA methylation (DNAm) has shown utility in indexing environmental exposures and could be leveraged to provide proxy signatures of chronic inflammation. Method We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 875 older adults (Lothian Birth Cohort 1936; mean age: 70 years) to develop a DNAm-based predictor. The predictor was tested in an independent cohort (Generation Scotland; N = 7028 [417 with measured IL-6], mean age: 51 years). Results A weighted score from 35 CpG sites optimally predicted IL-6 in the independent test set (Generation Scotland; R2 = 4.4%, p = 2.1 × 10−5). In the independent test cohort, both measured IL-6 and the DNAm proxy increased with age (serum IL-6: n = 417, β = 0.02, SE = 0.004, p = 1.3 × 10−7; DNAm IL-6 score: N = 7028, β = 0.02, SE = 0.0009, p < 2 × 10−16). Serum IL-6 did not associate with cognitive ability (n = 417, β = −0.06, SE = 0.05, p = .19); however, an inverse association was identified between the DNAm score and cognitive functioning (N = 7028, β = −0.16, SE = 0.02, pFDR < 2 × 10−16). Conclusions These results suggest methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for further insight into the relationship between inflammation and pertinent health outcomes.

scholarly journals Longitudinal Associations Between Loneliness and Cognitive Ability in the Lothian Birth Cohort 1936

2018 ◽  
Vol 74 (8) ◽  
pp. 1376-1386 ◽  
Author(s):  
Judith A Okely ◽  
Ian J Deary
Keyword(s):  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Verbal Memory ◽  
Cognitive Abilities ◽  
Birth Cohort Study ◽  
Visuospatial Ability ◽  
Lothian Birth Cohort ◽  
Longitudinal Associations ◽  
Reciprocal Associations

Abstract Objectives Loneliness is associated with poorer cognitive function in old age; however, the direction of this association is unknown. We tested for reciprocal associations between loneliness and the cognitive ability domains of processing speed, visuospatial ability, verbal memory, and crystallized ability. Method We used three triennial waves of longitudinal data from the Lothian Birth Cohort Study 1936, and tested for cross-lagged associations between loneliness and cognitive abilities using cross-lagged panel models. Results Better processing speed, visuospatial ability, or crystallized ability at age 73, was associated with less positive changes in loneliness between ages 73 and 76; however, these associations were not replicated between ages 76 and 79. Loneliness at ages 73 and 76 did not predict subsequent changes in cognitive abilities. Discussion Our findings indicate an association between cognitive ability and loneliness, such that individuals with lower cognitive abilities at age 73 may be at a slightly higher risk of becoming lonely. However, we did not find support for the hypothesis that loneliness causes a decline in cognitive health.

scholarly journals Creating and validating a DNA methylation-based proxy for Interleukin-6

2020 ◽  
Author(s):  
Anna J Stevenson ◽  
Danni A Gadd ◽  
Robert Francis Hillary ◽  
Daniel L. McCartney ◽  
Archie Campbell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Functioning ◽  
Cognitive Ability ◽  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Epigenetic Mechanism ◽  
Inverse Association ◽  
Age Related ◽  
Independent Test ◽  
Methylation Score

Chronic inflammation is a pervasive feature of ageing and may be linked to age-related cognitive decline. However, population studies evaluating its relationship with cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals' persisting levels of inflammation. The epigenetic mechanism DNA methylation has shown utility in indexing environmental exposures and could potentially be leveraged to provide proxy signatures of chronic inflammation. We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 895 older adults (mean age: 69 years) to develop a DNA methylation-based predictor. The predictor was tested in an independent cohort (n=7,028 [417 with measured IL-6], mean age: 51 years).We examined the association between the DNA methylation IL-6 score and serum IL-6, its association with age and established correlates of circulating IL-6, and with cognitive ability. A weighted score from 12 DNA methylation sites optimally predicted IL-6 (independent test set R2=5.1%). In the independent test cohort, both measured IL-6, and the DNA methylation proxy, increased as a function of age (serum IL-6: n=417, β=0.02, SE=0.004 p=1.3x10-7; DNAm IL-6 score: n=7,028, β=0.02, SE=0.0009, p<2x10-16). Serum IL-6 was not found to associate with cognitive ability (n=417, β=-0.06, SE=0.05, p=0.19); however, an inverse association was identified between the DNA methylation score and cognitive functioning (n=7,028, β=-0.14, SE=0.02, pFDR=1.5x10-14). These results suggest DNA methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for reliable insights into the relationship between chronic inflammation and pertinent health outcomes.

The association between cognitive ability across the lifespan and health literacy in old age: The Lothian Birth Cohort 1936

Intelligence ◽  
2011 ◽  
Vol 39 (4) ◽  
pp. 178-187 ◽  
Author(s):  
Catherine Murray ◽  
Wendy Johnson ◽  
Michael S. Wolf ◽  
Ian J. Deary
Keyword(s):  
Health Literacy ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Old Age ◽  
Lothian Birth Cohort

scholarly journals An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort

2019 ◽  
Vol 43 (9) ◽  
pp. 1795-1802 ◽  
Author(s):  
Olivia K. L. Hamilton ◽  
Qian Zhang ◽  
Allan F. McRae ◽  
Rosie M. Walker ◽  
Stewart W. Morris ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Physical Health ◽  
Birth Cohort ◽  
Poor Physical Health ◽  
Major Disease ◽  
Lothian Birth Cohort

Serum cholesterol and cognitive functions: the Lothian Birth Cohort 1936

2014 ◽  
Vol 27 (3) ◽  
pp. 439-453 ◽  
Author(s):  
Janie Corley ◽  
John M. Starr ◽  
Ian J. Deary
Keyword(s):  
Cognitive Function ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Old Age ◽  
Serum Cholesterol ◽  
Processing Speed ◽  
Verbal Ability ◽  
Older Age ◽  
Lothian Birth Cohort ◽  
Statin Use

ABSTRACTBackground:We examined the associations between serum cholesterol measures, statin use, and cognitive function measured in childhood and in old age. The possibility that lifelong (trait) cognitive ability accounts for any cross-sectional associations between cholesterol and cognitive performance in older age, seen in observational studies, has not been tested to date.Methods:Participants were 1,043 men and women from the Lothian Birth Cohort 1936 Study, most of whom had participated in a nationwide IQ-type test in childhood (Scottish Mental Survey of 1947), and were followed up at about age 70 years. Serum cholesterol measures included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and cholesterol:HDL cholesterol ratio. Cognitive outcome measures were age 70 IQ (using the same test as at age 11 years), general cognitive ability (g), processing speed, memory, and verbal ability.Results:Higher TC, higher HDL-C, and lower triglycerides were associated with higher age 70 cognitive scores in most cognitive domains. These relationships were no longer significant after covarying for childhood IQ, with the exception a markedly attenuated association between TC and processing speed, and triglycerides and age 70 IQ. In the fully adjusted model, all conventionally significant (p < 0.05) effects were removed. Childhood IQ predicted statin use in old age. Statin users had lower g, processing speed, and verbal ability scores at age 70 years after covarying for childhood IQ, but significance was lost after adjusting for TC levels.Conclusions:These results suggest that serum cholesterol and cognitive function are associated in older age via the lifelong stable trait of intelligence. Potential mechanisms, including lifestyle factors, are discussed.

scholarly journals Retinal nerve fiber layer thickness and cognitive ability in older people: the Lothian Birth Cohort 1936 study

2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Augustinus Laude ◽  
Gerassimos Lascaratos ◽  
Ross D Henderson ◽  
John M Starr ◽  
Ian J Deary ◽  
...  
Keyword(s):  
Older People ◽  
Cognitive Ability ◽  
Nerve Fiber ◽  
Layer Thickness ◽  
Birth Cohort ◽  
Retinal Nerve Fiber Layer ◽  
Fiber Layer ◽  
Nerve Fiber Layer ◽  
Nerve Fiber Layer Thickness ◽  
Lothian Birth Cohort
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