The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of ... more The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of domains in dementia. Identifying the order in which cognitive decline occurs across items, and whether this varies between dementia aetiologies could add more information to subdomain scores. ACE-Revised data from 350 patients were split into three groups: Alzheimer's type (n = 131), predominantly frontal (n = 119) and other frontotemporal lobe degenerative disorders (n = 100). Results of factor analysis and Mokken scaling analysis were compared. Principal component analysis revealed one factor for each group. Confirmatory factor analysis found that the one-factor model fit two samples poorly. Mokken analyses revealed different item ordering in terms of difficulty for each group. The different patterns for each diagnostic group could aid in the separation of these different types of dementia.
Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with m... more Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 partic...
The British journal of psychiatry : the journal of mental science, 2014
That risk factors measured in middle age may not fully explain future dementia risk implicates ex... more That risk factors measured in middle age may not fully explain future dementia risk implicates exposures acting earlier in life. Height may capture early-life illness, adversity, nutrition and psychosocial stress. To investigate the little-explored association between height and dementia death. Method Individual participant meta-analysis using 18 prospective general population cohort studies with identical methodologies (1994-2008; n = 181 800). Mean follow-up of 9.8 years gave rise to 426 and 667 dementia deaths in men and women respectively. The mean heights were 174.4 cm (s.d. = 7.3) for men and 161.0 cm (s.d. = 6.8) for women. In analyses taking into account multiple covariates, increasing height was related to lower rates of death from dementia in a dose-response pattern (P ⩽ 0.01 for trend). There was evidence of a differential effect by gender (P = 0.016 for interaction). Thus, the association observed in men (hazard ratio per s.d. decrease in height 1.24, 95% CI 1.11-1.39) w...
The British journal of psychiatry : the journal of mental science, Jan 13, 2014
Background People with dementia are extremely vulnerable in hospital and unscheduled admissions s... more Background People with dementia are extremely vulnerable in hospital and unscheduled admissions should be avoided if possible. Aims To identify any predictors of general hospital admission in people with dementia in a well-characterised national prospective cohort study. Method A cohort of 730 persons with dementia was drawn from the Scottish Dementia Research Interest Register (47.8% female; mean age 76.3 years, s.d. = 8.2, range 50-94), with a mean follow-up period of 1.2 years. Results In the age- and gender-adjusted multivariable model (n = 681; 251 admitted), Neuropsychiatric Inventory score (hazard ratio per s.d. disadvantage 1.21, 95% CI 1.08-1.36) was identified as an independent predictor of admission to hospital. Conclusions Neuropsychiatric symptoms in dementia, measured using the Neuropsychiatric Inventory, predict non-psychiatric hospital admission of people with dementia. Further studies are merited to test whether interventions to reduce such symptoms might reduce uns...
There is some evidence that people who score higher on tests of intelligence in childhood have lo... more There is some evidence that people who score higher on tests of intelligence in childhood have lower carotid intima-media thickness and higher ankle brachial index in middle age. These findings need replicating in other, older populations. We investigated the prospective relationship between intelligence in childhood and atherosclerosis in the carotid and peripheral arteries at age 73 years. Participants were 713 members of the Lothian Birth Cohort 1936 whose intelligence was assessed at age 11 years. At age 73 years, carotid intima-media thickness and degree of stenosis were measured using ultrasound imaging; ankle-brachial index was measured using Doppler ultrasound. There were no significant associations between intelligence at age 11 and measures of atherosclerosis at age 73. In age- and sex-adjusted analyses, for a standard deviation higher score in intelligence, intima-media thickness (x 10) was lower by 0.07 (-0.20, 0.06) mm and ankle brachial index (x 10) was lower by 0.09 (...
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 7, 2015
Cognitive deficits and reduced educational achievement are common in psychiatric illness; underst... more Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals ...
Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. I... more Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the mole...
Aging-related changes occur for multiple domains of cognitive functioning. An accumulating body o... more Aging-related changes occur for multiple domains of cognitive functioning. An accumulating body of research indicates that, rather than representing statistically independent phenomena, aging-related cognitive changes are moderately to strongly correlated across domains. However, previous studies have typically been conducted in age-heterogeneous samples over longitudinal time lags of 6 or more years, and have failed to consider whether results are robust to a comprehensive set of controls. Capitalizing on 3-year longitudinal data from the Lothian Birth Cohort of 1936, we took a longitudinal narrow age cohort approach to examine cross-domain cognitive change interrelations from ages 70 to 73 years. We fit multivariate latent difference score models to factors representing visuospatial ability, processing speed, memory, and crystallized ability. Changes were moderately interrelated, with a general factor of change accounting for 47% of the variance in changes across domains. Change i...
... mental health2,; John Starr, consultant and senior lecturer3,; Ian J Deary, professor of diff... more ... mental health2,; John Starr, consultant and senior lecturer3,; Ian J Deary, professor of differential psychology (Ian.Deary{at}ed.ac.uk)1. 1 Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ; 2 Department of ...
Journal of epidemiology and community health, Jan 17, 2015
In addition to being associated with all-cause mortality and cardiovascular disease mortality, lu... more In addition to being associated with all-cause mortality and cardiovascular disease mortality, lung function has been linked with dementia. However, existing studies typically provide imprecise estimates due to small numbers of outcome events and are based on unrepresentative samples of the general population. Individual participant meta-analysis of six cohort studies from the Health Survey for England and the Scottish Health Survey (total N=54 671). Dementia-related mortality was identified by mention of dementia on any part of the death certificate (mean follow-up 11.7 years). Study-specific Cox proportional hazard models of the association between lung function and dementia-related death were pooled using random effect meta-analysis to produce overall results. There was a dose-response association between poorer lung function and a higher risk of dementia-related death (age- and sex-adjusted HR compared to highest quartile of forced expiratory volume in 1 s (FEV1), 95% CI: second...
Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities wh... more Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities which may be influenced by an overlapping set of genetic variants. Genome-wide complex trait analysis estimates that common genetic variants account for about 24% of the variation contributing to liability for AD. It is also estimated that 24% of the variance of non-pathological cognitive aging is accounted for by common single nucleotide polymorphisms. However, although the APOE locus is associated with both AD and cognitive aging, it is not known to what extent other common genetic variants, with smaller effect sizes that influence both, overlap. We test the hypothesis that polygenic risk for AD is associated with cognitive ability and cognitive change in about 3,000 non-demented older people (Cognitive Ageing Genetics England and Scotland-CAGES-consortium). We found no significant association of polygenic risk for AD with cognitive ability or cognitive change in CAGES, indicating that t...
We examined the associations between serum cholesterol measures, statin use, and cognitive functi... more 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. 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. 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. 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.
Epigenetic mechanisms such as DNA methylation (DNAm) are essential for regulation of gene express... more Epigenetic mechanisms such as DNA methylation (DNAm) are essential for regulation of gene expression. DNAm is dynamic, influenced by both environmental and genetic factors. Epigenetic drift is the divergence of the epigenome as a function of age due to stochastic changes in methylation. Here we show that epigenetic drift may be constrained at many CpGs across the human genome by DNA sequence variation and by lifetime environmental exposures. We estimate repeatability of DNAm at 234,811 autosomal CpGs in whole blood using longitudinal data (2-3 repeated measurements) on 478 older people from two Scottish birth cohorts--the Lothian Birth Cohorts of 1921 and 1936. Median age was 79 yr and 70 yr, and the follow-up period was ∼10 yr and ∼6 yr, respectively. We compare this to methylation heritability estimated in the Brisbane Systems Genomics Study, a cross-sectional study of 117 families (offspring median age 13 yr; parent median age 46 yr). CpG repeatability in older people was highly ...
International journal of epidemiology, Jan 22, 2015
The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, ... more The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a ...
The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of ... more The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of domains in dementia. Identifying the order in which cognitive decline occurs across items, and whether this varies between dementia aetiologies could add more information to subdomain scores. ACE-Revised data from 350 patients were split into three groups: Alzheimer's type (n = 131), predominantly frontal (n = 119) and other frontotemporal lobe degenerative disorders (n = 100). Results of factor analysis and Mokken scaling analysis were compared. Principal component analysis revealed one factor for each group. Confirmatory factor analysis found that the one-factor model fit two samples poorly. Mokken analyses revealed different item ordering in terms of difficulty for each group. The different patterns for each diagnostic group could aid in the separation of these different types of dementia.
Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with m... more Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 partic...
The British journal of psychiatry : the journal of mental science, 2014
That risk factors measured in middle age may not fully explain future dementia risk implicates ex... more That risk factors measured in middle age may not fully explain future dementia risk implicates exposures acting earlier in life. Height may capture early-life illness, adversity, nutrition and psychosocial stress. To investigate the little-explored association between height and dementia death. Method Individual participant meta-analysis using 18 prospective general population cohort studies with identical methodologies (1994-2008; n = 181 800). Mean follow-up of 9.8 years gave rise to 426 and 667 dementia deaths in men and women respectively. The mean heights were 174.4 cm (s.d. = 7.3) for men and 161.0 cm (s.d. = 6.8) for women. In analyses taking into account multiple covariates, increasing height was related to lower rates of death from dementia in a dose-response pattern (P ⩽ 0.01 for trend). There was evidence of a differential effect by gender (P = 0.016 for interaction). Thus, the association observed in men (hazard ratio per s.d. decrease in height 1.24, 95% CI 1.11-1.39) w...
The British journal of psychiatry : the journal of mental science, Jan 13, 2014
Background People with dementia are extremely vulnerable in hospital and unscheduled admissions s... more Background People with dementia are extremely vulnerable in hospital and unscheduled admissions should be avoided if possible. Aims To identify any predictors of general hospital admission in people with dementia in a well-characterised national prospective cohort study. Method A cohort of 730 persons with dementia was drawn from the Scottish Dementia Research Interest Register (47.8% female; mean age 76.3 years, s.d. = 8.2, range 50-94), with a mean follow-up period of 1.2 years. Results In the age- and gender-adjusted multivariable model (n = 681; 251 admitted), Neuropsychiatric Inventory score (hazard ratio per s.d. disadvantage 1.21, 95% CI 1.08-1.36) was identified as an independent predictor of admission to hospital. Conclusions Neuropsychiatric symptoms in dementia, measured using the Neuropsychiatric Inventory, predict non-psychiatric hospital admission of people with dementia. Further studies are merited to test whether interventions to reduce such symptoms might reduce uns...
There is some evidence that people who score higher on tests of intelligence in childhood have lo... more There is some evidence that people who score higher on tests of intelligence in childhood have lower carotid intima-media thickness and higher ankle brachial index in middle age. These findings need replicating in other, older populations. We investigated the prospective relationship between intelligence in childhood and atherosclerosis in the carotid and peripheral arteries at age 73 years. Participants were 713 members of the Lothian Birth Cohort 1936 whose intelligence was assessed at age 11 years. At age 73 years, carotid intima-media thickness and degree of stenosis were measured using ultrasound imaging; ankle-brachial index was measured using Doppler ultrasound. There were no significant associations between intelligence at age 11 and measures of atherosclerosis at age 73. In age- and sex-adjusted analyses, for a standard deviation higher score in intelligence, intima-media thickness (x 10) was lower by 0.07 (-0.20, 0.06) mm and ankle brachial index (x 10) was lower by 0.09 (...
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 7, 2015
Cognitive deficits and reduced educational achievement are common in psychiatric illness; underst... more Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals ...
Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. I... more Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the mole...
Aging-related changes occur for multiple domains of cognitive functioning. An accumulating body o... more Aging-related changes occur for multiple domains of cognitive functioning. An accumulating body of research indicates that, rather than representing statistically independent phenomena, aging-related cognitive changes are moderately to strongly correlated across domains. However, previous studies have typically been conducted in age-heterogeneous samples over longitudinal time lags of 6 or more years, and have failed to consider whether results are robust to a comprehensive set of controls. Capitalizing on 3-year longitudinal data from the Lothian Birth Cohort of 1936, we took a longitudinal narrow age cohort approach to examine cross-domain cognitive change interrelations from ages 70 to 73 years. We fit multivariate latent difference score models to factors representing visuospatial ability, processing speed, memory, and crystallized ability. Changes were moderately interrelated, with a general factor of change accounting for 47% of the variance in changes across domains. Change i...
... mental health2,; John Starr, consultant and senior lecturer3,; Ian J Deary, professor of diff... more ... mental health2,; John Starr, consultant and senior lecturer3,; Ian J Deary, professor of differential psychology (Ian.Deary{at}ed.ac.uk)1. 1 Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ; 2 Department of ...
Journal of epidemiology and community health, Jan 17, 2015
In addition to being associated with all-cause mortality and cardiovascular disease mortality, lu... more In addition to being associated with all-cause mortality and cardiovascular disease mortality, lung function has been linked with dementia. However, existing studies typically provide imprecise estimates due to small numbers of outcome events and are based on unrepresentative samples of the general population. Individual participant meta-analysis of six cohort studies from the Health Survey for England and the Scottish Health Survey (total N=54 671). Dementia-related mortality was identified by mention of dementia on any part of the death certificate (mean follow-up 11.7 years). Study-specific Cox proportional hazard models of the association between lung function and dementia-related death were pooled using random effect meta-analysis to produce overall results. There was a dose-response association between poorer lung function and a higher risk of dementia-related death (age- and sex-adjusted HR compared to highest quartile of forced expiratory volume in 1 s (FEV1), 95% CI: second...
Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities wh... more Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities which may be influenced by an overlapping set of genetic variants. Genome-wide complex trait analysis estimates that common genetic variants account for about 24% of the variation contributing to liability for AD. It is also estimated that 24% of the variance of non-pathological cognitive aging is accounted for by common single nucleotide polymorphisms. However, although the APOE locus is associated with both AD and cognitive aging, it is not known to what extent other common genetic variants, with smaller effect sizes that influence both, overlap. We test the hypothesis that polygenic risk for AD is associated with cognitive ability and cognitive change in about 3,000 non-demented older people (Cognitive Ageing Genetics England and Scotland-CAGES-consortium). We found no significant association of polygenic risk for AD with cognitive ability or cognitive change in CAGES, indicating that t...
We examined the associations between serum cholesterol measures, statin use, and cognitive functi... more 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. 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. 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. 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.
Epigenetic mechanisms such as DNA methylation (DNAm) are essential for regulation of gene express... more Epigenetic mechanisms such as DNA methylation (DNAm) are essential for regulation of gene expression. DNAm is dynamic, influenced by both environmental and genetic factors. Epigenetic drift is the divergence of the epigenome as a function of age due to stochastic changes in methylation. Here we show that epigenetic drift may be constrained at many CpGs across the human genome by DNA sequence variation and by lifetime environmental exposures. We estimate repeatability of DNAm at 234,811 autosomal CpGs in whole blood using longitudinal data (2-3 repeated measurements) on 478 older people from two Scottish birth cohorts--the Lothian Birth Cohorts of 1921 and 1936. Median age was 79 yr and 70 yr, and the follow-up period was ∼10 yr and ∼6 yr, respectively. We compare this to methylation heritability estimated in the Brisbane Systems Genomics Study, a cross-sectional study of 117 families (offspring median age 13 yr; parent median age 46 yr). CpG repeatability in older people was highly ...
International journal of epidemiology, Jan 22, 2015
The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, ... more The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a ...
Uploads
Papers by John Starr