scholarly journals An epigenetic predictor of death captures multi-modal measures of brain health

2019 ◽  
Author(s):  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
Simon R. Cox ◽  
Daniel L. McCartney ◽  
Sarah E. Harris ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Epigenetic Mechanism ◽  
Vascular Lesions ◽  
Epigenetic Clock ◽  
General Cognitive Ability ◽  
Brain Health ◽  
Standard Deviation Increase ◽  
Brain White Matter ◽  
Age Related ◽  
Lothian Birth Cohort

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm) – a commonly studied epigenetic mechanism. A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as a number of age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n=709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over twelve years of follow-up (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (β=-0.11), lower age 73 general cognitive ability (β=-0.18), decreased brain volume (β=-0.25) and increased brain white matter hyperintensities (β=0.17). Sixty-eight of 137 health- and brain-related phenotypes tested were significantly associated with DNAm GrimAge. Adjusting all models for childhood cognitive ability attenuated to non-significance a small number of associations (12/68 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge cross-sectionally associates with lower cognitive ability and brain vascular lesions in older age, independently of early life cognitive ability. Thus, this epigenetic predictor of mortality is also associated with multiple different measures of brain health and may aid in the prediction of age-related cognitive decline.

scholarly journals An epigenetic predictor of death captures multi-modal measures of brain health

2019 ◽  
Author(s):  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
Simon R. Cox ◽  
Daniel L. McCartney ◽  
Sarah E. Harris ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Vascular Lesions ◽  
Epigenetic Clock ◽  
General Cognitive Ability ◽  
Brain Health ◽  
Standard Deviation Increase ◽  
Brain White Matter ◽  
Age Related ◽  
Tentative Evidence

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10−16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = −0.11), lower age 73 general cognitive ability (β = −0.18), decreased brain volume (β = −0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

Associating emotions with Wagner’s music: A developmental perspective

2016 ◽  
Vol 45 (5) ◽  
pp. 752-760 ◽  
Author(s):  
Paulo E. Andrade ◽  
Patrícia Vanzella ◽  
Olga V. C. A. Andrade ◽  
E. Glenn Schellenberg
Keyword(s):  
Academic Achievement ◽  
Young Children ◽  
University Students ◽  
Cognitive Ability ◽  
Dimensional Space ◽  
Two Dimensional ◽  
General Cognitive Ability ◽  
Music Training ◽  
Age Related ◽  
Musical Excerpts

Brazilian listeners ( N = 303) were asked to identify emotions conveyed in 1-min instrumental excerpts from Wagner’s operas. Participants included musically untrained 7- to 10-year-olds and university students in music (musicians) or science (nonmusicians). After hearing each of eight different excerpts, listeners made a forced-choice judgment about which of eight emotions best matched the excerpt. The excerpts and emotions were chosen so that two were in each of four quadrants in two-dimensional space as defined by arousal and valence. Listeners of all ages performed at above-chance levels, which means that complex, unfamiliar musical materials from a different century and culture are nevertheless meaningful for young children. In fact, children performed similarly to adult nonmusicians. There was age-related improvement among children, however, and adult musicians performed best of all. As in previous research that used simpler musical excerpts, effects due to age and music training were due primarily to improvements in selecting the appropriate valence. That is, even 10-year-olds with no music training were as likely as adult musicians to match a high- or low-arousal excerpt with a high- or low-arousal emotion, respectively. Performance was independent of general cognitive ability as measured by academic achievement but correlated positively with basic pitch-perception skills.

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.

scholarly journals Fluid Intelligence Predicts Change in Depressive Symptoms in Later Life: The Lothian Birth Cohort 1936

2018 ◽  
Vol 29 (12) ◽  
pp. 1984-1995 ◽  
Author(s):  
Stephen Aichele ◽  
Paolo Ghisletta ◽  
Janie Corley ◽  
Alison Pattie ◽  
Adele M. Taylor ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Birth Cohort ◽  
Fluid Intelligence ◽  
Coupling Effect ◽  
Coupling Parameter ◽  
Later Life ◽  
Community Dwelling ◽  
Standard Deviation Increase ◽  
Age Related ◽  
Lothian Birth Cohort

We examined reciprocal, time-ordered associations between age-related changes in fluid intelligence and depressive symptoms. Participants were 1,091 community-dwelling older adults from the Lothian Birth Cohort 1936 study who were assessed repeatedly at 3-year intervals between the ages of 70 and 79 years. On average, fluid intelligence and depressive symptoms worsened with age. There was also a dynamic-coupling effect, in which low fluid intelligence at a given age predicted increasing depressive symptoms across the following 3-year interval, whereas the converse did not hold. Model comparisons showed that this coupling parameter significantly improved overall fit and had a correspondingly moderately strong effect size, accounting on average for an accumulated 0.9 standard-deviation increase in depressive symptoms, following lower cognitive performance, across the observed age range. Adjustment for sociodemographic and health-related covariates did not significantly attenuate this association. This implies that monitoring for cognitive decrements in later life may expedite interventions to reduce related increases in depression risk.

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

2019 ◽  
Vol 74 (2) ◽  
pp. 108-113 ◽  
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.

scholarly journals Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
O. K. L. Hamilton ◽  
S. R. Cox ◽  
J. A. Okely ◽  
F. Conte ◽  
L. Ballerini ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
General Cognitive Ability ◽  
Vessel Disease ◽  
Lothian Birth Cohort

AbstractSlowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

scholarly journals Impact of COVID-19 lockdown on psychosocial factors, health, and lifestyle in Scottish octogenarians: The Lothian Birth Cohort 1936 study

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253153
Author(s):  
Adele M. Taylor ◽  
Danielle Page ◽  
Judith A. Okely ◽  
Janie Corley ◽  
Miles Welstead ◽  
...  
Keyword(s):  
Mental Health ◽  
Physical Activity ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Psychosocial Factors ◽  
Emotional Stability ◽  
General Cognitive Ability ◽  
Physical And Mental Health ◽  
Occupational Class ◽  
Lothian Birth Cohort

Background Little is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group. Methods Lothian Birth Cohort 1936 members, residing mostly in Edinburgh and the surrounding Lothians regions in Scotland, mean age 84 years (SD = 0.3), responded to an online questionnaire in May 2020 (n = 190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes. Results Four respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR = 0.71, 95%CI 0.51–0.98) and poorer self-rated general health (OR = 0.62, 95%CI 0.42–0.92). Increased internet use associated with female sex (OR = 2.32, 95%CI 1.12–4.86) and higher general cognitive ability (OR = 1.53, 95%CI 1.03–2.33). Loneliness associated with living alone (OR = 0.15, 95%CI 0.07–0.31) and greater anxiety symptoms (OR = 1.76, 95%CI 0.45–1.24). COVID-19 related stress associated with lower emotional stability scores (OR = 0.40, 95%CI 0.24–0.62). Decreased physical activity associated with less professional occupational class (OR = 1.43, 95%CI 1.04–1.96), and lower general cognitive ability (OR = 0.679, 95%CI 0.491–0.931). Conclusions Characteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes.

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

2019 ◽  
Author(s):  
Catharine R Gale ◽  
Stuart James Ritchie ◽  
Ian 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

Background: Physical frailty is associated with many adverse outcomes including disability, chronic disease, hospitalization, institutionalization 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. Method: Participants were 950 members of the Lothian Birth Cohort 1936. Physical frailty was assessed at age 70 using the Fried criteria. Cognitive function was assessed at ages 70, 73, 76 and 79. We used linear regression to examine the associations between physical frailty status at age 70 and factor score estimates for baseline level of and change in four cognitive domains (visuospatial ability, memory, processing speed, and crystallized ability) and in general cognitive ability.Results: Physical frailty, but not pre-frailty, 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- and sex-adjusted standardized regression coefficients (95% confidence intervals) were: -0.45 (-0.70, -0.20) for visuospatial ability, -0.32 (-0.56, -0.07) for memory, -0.47 (-0.72, -0.22) for processing speed, -0.43 (-0.68, -0.18) for crystallized ability, and -0.45 (-0.70, -0.21) for general cognitive ability. Further adjustment for the other covariates had only modest attenuating effects on these associations and they remained significant.Conclusion: Physical frailty may be an important indicator of age-related decline across multiple cognitive domains.

scholarly journals Neurology-related protein biomarkers are associated with general fluid cognitive ability and brain volume in older age

2019 ◽  
Author(s):  
Sarah E. Harris ◽  
Simon R. Cox ◽  
Steven Bell ◽  
Riccardo E. Marioni ◽  
Bram P Prins ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Birth Cohort ◽  
Plasma Levels ◽  
Brain Volume ◽  
Later Life ◽  
Effect Sizes ◽  
Total Brain Volume ◽  
Age Related ◽  
Lothian Birth Cohort ◽  
Related Proteins

AbstractIdentifying the biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. This study investigated the associations between plasma levels of 91 neurology-related proteins (Olink® Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N=798), the Lothian Birth Cohort 1921 (LBC1921, N=165), and the INTERVAL BioResource, (N=4,451). In LBC1936, we also examined mediation of protein-cognitive ability associations by MRI-derived indices of brain structure. In the LBC1936, 22 of the proteins and the first principal component (PC) created from a PC analysis of the 91 proteins, were associated with general fluid cognitive ability (β between −0.11 and −0.17, p<0.0029). Total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. Effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936 in an age-matched subsample of INTERVAL. Similar effect sizes were found for the majority of these 22 proteins in the older LBC1921. The associations were not replicated in a younger subset of INTERVAL. In conclusion, we identified plasma levels of a number of neurology-related proteins that were associated with general fluid cognitive ability in later life, some of which were mediated by brain volume.

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