DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936

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.

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

International Journal of Obesity ◽

10.1038/s41366-018-0262-3 ◽

2019 ◽

Vol 43 (9) ◽

pp. 1795-1802 ◽

Cited By ~ 3

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

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Dietary iodine exposure and brain structures and cognition in older people. Exploratory analysis in the Lothian Birth Cohort 1936

The journal of nutrition health & aging ◽

10.1007/s12603-017-0954-8 ◽

2017 ◽

Vol 21 (9) ◽

pp. 971-979 ◽

Cited By ~ 5

Author(s):

Maria del C. Valdés Hernández ◽

J. Kyle ◽

J. Allan ◽

M. Allerhand ◽

H. Clark ◽

...

Keyword(s):

Older People ◽

Birth Cohort ◽

Brain Structures ◽

Exploratory Analysis ◽

Lothian Birth Cohort

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

BMC Ophthalmology ◽

10.1186/1471-2415-13-28 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 7

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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Epigenetic signatures of smoking associate with cognitive function, brain structure, and mental and physical health outcomes in the Lothian Birth Cohort 1936

Translational Psychiatry ◽

10.1038/s41398-019-0576-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Janie Corley ◽

Simon R. Cox ◽

Sarah E. Harris ◽

Maria Valdéz Hernandez ◽

Susana Muñoz Maniega ◽

...

Keyword(s):

Dna Methylation ◽

Cognitive Function ◽

Health Outcomes ◽

Physical Health ◽

Birth Cohort ◽

Smoking Status ◽

Brain Mri ◽

Smoking Exposure ◽

Eta Squared ◽

Lothian Birth Cohort

Abstract Recent advances in genome-wide DNA methylation (DNAm) profiling for smoking behaviour have given rise to a new, molecular biomarker of smoking exposure. It is unclear whether a smoking-associated DNAm (epigenetic) score has predictive value for ageing-related health outcomes which is independent of contributions from self-reported (phenotypic) smoking measures. Blood DNA methylation levels were measured in 895 adults aged 70 years in the Lothian Birth Cohort 1936 (LBC1936) study using the Illumina 450K assay. A DNA methylation score based on 230 CpGs was used as a proxy for smoking exposure. Associations between smoking variables and health outcomes at age 70 were modelled using general linear modelling (ANCOVA) and logistic regression. Additional analyses of smoking with brain MRI measures at age 73 (n = 532) were performed. Smoking-DNAm scores were positively associated with self-reported smoking status (P < 0.001, eta-squared ɳ2 = 0.63) and smoking pack years (r = 0.69, P < 0.001). Higher smoking DNAm scores were associated with variables related to poorer cognitive function, structural brain integrity, physical health, and psychosocial health. Compared with phenotypic smoking, the methylation marker provided stronger associations with all of the cognitive function scores, especially visuospatial ability (P < 0.001, partial eta-squared ɳp2 = 0.022) and processing speed (P < 0.001, ɳp2 = 0.030); inflammatory markers (all P < 0.001, ranges from ɳp2 = 0.021 to 0.030); dietary patterns (healthy diet (P < 0.001, ɳp2 = 0.052) and traditional diet (P < 0.001, ɳp2 = 0.032); stroke (P = 0.006, OR 1.48, 95% CI 1.12, 1.96); mortality (P < 0.001, OR 1.59, 95% CI 1.42, 1.79), and at age 73; with MRI volumetric measures (all P < 0.001, ranges from ɳp2 = 0.030 to 0.052). Additionally, education was the most important life-course predictor of lifetime smoking tested. Our results suggest that a smoking-associated methylation biomarker typically explains a greater proportion of the variance in some smoking-related morbidities in older adults, than phenotypic measures of smoking exposure, with some of the accounted-for variance being independent of phenotypic smoking status.

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Physical frailty and decline in general and specific cognitive abilities: the Lothian Birth Cohort 1936

Journal of Epidemiology & Community Health ◽

10.1136/jech-2019-213280 ◽

2019 ◽

Vol 74 (2) ◽

pp. 108-113 ◽

Cited By ~ 3

Author(s):

Catharine Gale ◽

Stuart J Ritchie ◽

John M Starr ◽

Ian J Deary

Keyword(s):

Cognitive Ability ◽

Birth Cohort ◽

Processing Speed ◽

Cognitive Abilities ◽

General Cognitive Ability ◽

Visuospatial Ability ◽

Physical Frailty ◽

Cognitive Domains ◽

Memory Processing ◽

Lothian Birth Cohort

BackgroundPhysical frailty is associated with many adverse outcomes including disability, chronic disease, hospitalisation, institutionalisation and death. It is unclear what impact it might have on the rate of normal cognitive ageing. We investigated whether physical frailty was related to initial level of, and change in, cognitive abilities from age 70 to 79 years.MethodParticipants were 950 members of the Lothian Birth Cohort 1936. Physical frailty was assessed at age 70 years using the Fried criteria. Cognitive function was assessed at ages 70, 73, 76 and 79 years. We used linear regression to examine cross-sectional and prospective associations between physical frailty status at age 70 years and factor score estimates for baseline level of and change in four cognitive domains (visuospatial ability, memory, processing speed and crystallised ability) and in general cognitive ability.ResultsPhysical frailty, but not prefrailty, was associated with lower baseline levels of visuospatial ability, memory, processing speed and general cognitive ability after control for age, sex, education, depressive symptoms, smoking and number of chronic illnesses. Physical frailty was associated with greater decline in each cognitive domain: age-adjusted and sex-adjusted standardised regression coefficients (95% CIs) were: −0.45 (−0.70 to –0.20) for visuospatial ability, −0.32 (−0.56 to –0.07) for memory, −0.47 (−0.72 to −0.22) for processing speed, −0.43 (−0.68 to –0.18) for crystallised ability and −0.45 (−0.70 to –0.21) for general cognitive ability. These associations were only slightly attenuated after additional control for other covariates.ConclusionPhysical frailty may be an important indicator of age-related decline across multiple cognitive domains.

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DNA methylation-based measures of accelerated biological ageing and the risk of dementia in the oldest-old: a study of the Lothian Birth Cohort 1921

BMC Psychiatry ◽

10.1186/s12888-020-2469-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Ruth A. Sibbett ◽

Drew M. Altschul ◽

Riccardo E. Marioni ◽

Ian J. Deary ◽

John M. Starr ◽

...

Keyword(s):

Dna Methylation ◽

Birth Cohort ◽

Oldest Old ◽

Biological Ageing ◽

Lothian Birth Cohort

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The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

International Journal of Epidemiology ◽

10.1093/ije/dyu277 ◽

2015 ◽

Vol 44 (4) ◽

pp. 1388-1396 ◽

Cited By ~ 260

Author(s):

Riccardo E Marioni ◽

Sonia Shah ◽

Allan F McRae ◽

Stuart J Ritchie ◽

Graciela Muniz-Terrera ◽

...

Keyword(s):

Birth Cohort ◽

Epigenetic Clock ◽

Lothian Birth Cohort

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Change in Physical Activity, Sleep Quality, and Psychosocial Variables during COVID-19 Lockdown: Evidence from the Lothian Birth Cohort 1936

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18010210 ◽

2020 ◽

Vol 18 (1) ◽

pp. 210

Author(s):

Judith A. Okely ◽

Janie Corley ◽

Miles Welstead ◽

Adele M. Taylor ◽

Danielle Page ◽

...

Keyword(s):

Physical Activity ◽

Social Support ◽

Sleep Quality ◽

Older People ◽

Birth Cohort ◽

Mental Wellbeing ◽

Psychosocial Variables ◽

Cross Sectional ◽

Lothian Birth Cohort ◽

History Of

(1) Objectives: The COVID-19 pandemic has disproportionately affected the lives of older people. In this study, we examine changes in physical activity, sleep quality, and psychosocial variables among older people during COVID-19 lockdown. We build on cross-sectional studies on this topic by assessing change longitudinally. We also examined whether participant characteristics including demographic, cognitive, personality, and health variables were related to more positive or negative changes during lockdown. (2) Methods: 137 older participants (mean age 84 years) from the Lothian Birth Cohort 1936 study were included in the analysis. They completed the same questionnaires assessing physical activity, sleep quality, mental wellbeing, social support, loneliness, neighbourhood cohesion, and memory problems before (mostly 2 years earlier) and again during national lockdown. (3) Results: On average, levels of physical activity were reduced (those doing minimal physical activity increased from 10% to 19%) and perceived social support increased during lockdown (effect size drm = 0.178). More positive change in the psychosocial and behavioural outcome variables during lockdown was associated with personality traits (greater intellect, emotional stability, and extraversion) and having a higher general cognitive ability. Participants with a history of cardiovascular disease, more symptoms of anxiety, or who lived alone were more likely to experience negative changes in the outcome variables during lockdown. (4) Discussion: These results provide further insight into the experiences of older people during the COVID-19 pandemic and could help to identify those at greatest risk of negative psychosocial or behavioural changes during this time.

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