Lothian Birth Cohort 1936 whole genome sequencing study
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PROVIDER: EGAS00001003819 | EGA |
REPOSITORIES: EGA
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Project description:297 members of the Lothian Birth Cohort 1921 (LBC1921) were sequenced using the Illumina HiSeq X platform. The LBC1921 are a relatively healthy cohort of 550 individuals who underwent cognitive and medical testing at a mean age of 79.1 (SD=0.6) years. They have since undergone four further waves of testing, approximately three years apart.
| EGAS00001003818 | EGA
Project description:The repeatability of longitudinal measures of whole blood DNA methylation (obtained using the Illumina 450k chip) was assessed in two cohorts of ageing. The Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936. Data were collected at ages 70, 73, and 76 (LBC1936) and 79, 87, 90 (LBC1921) with 478 participants having two or more measures of methylation.
| EGAS00001000910 | EGA
Project description:BackgroundThe Lothian Birth Cohort 1936 (LBC1936) is a highly phenotyped longitudinal study of cognitive and brain ageing. Given its substantial clinical importance, we derived an indicator of mild cognitive impairment (MCI) and amnestic and nonamnestic subtypes at 3 time points.MethodsMCI status was derived at 3 waves of the LBC1936 at ages 76 (n=567), 79 (n=441), and 82 years (n=341). A general MCI category was derived as well as amnestic MCI (aMCI) and nonamnestic MCI (naMCI). A comparison was made between MCI derivations using normative data from the LBC1936 cohort versus the general UK population.ResultsMCI rates showed a proportional increase at each wave between 76 and 82 years from 15% to 18%. Rates of MCI subtypes also showed a proportional increase over time: aMCI 4% to 6%; naMCI 12% to 16%. Higher rates of MCI were found when using the LBC1936 normative data to derive MCI classification rather than UK-wide norms.ConclusionsWe found that MCI and aMCI rates in the LBC1936 were consistent with previous research. However, naMCI rates were higher than expected. Future LBC1936 research should assess the predictive factors associated with MCI prevalence to validate previous findings and identify novel risk factors.
| S-EPMC8386587 | biostudies-literature
Project description:Elevated serum and cerebrospinal fluid concentrations of S100?, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, although concentrations are also influenced by several other factors. The longitudinal association between serum S100? concentrations and brain health in nonpathological aging is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100? and brain MRI parameters: white matter hyperintensities, perivascular space visibility, white matter fractional anisotropy and mean diffusivity (MD), global atrophy, and gray matter volume. Using bivariate change score structural equation models, correcting for age, sex, diabetes, and hypertension, higher S100? was cross-sectionally associated with poorer general fractional anisotropy (r = -0.150, p = 0.001), which was strongest in the anterior thalamic (r = -0.155, p < 0.001) and cingulum bundles (r = -0.111, p = 0.005), and survived false discovery rate correction. Longitudinally, there were no significant associations between changes in brain imaging parameters and S100? after false discovery rate correction. These data provide some weak evidence that S100? may be an informative biomarker of brain white matter aging.
| S-EPMC6075468 | biostudies-literature
Project description:The presence of an apolipoprotein E (APOE) ε4 allele, lower physical fitness, smoking, and lower serum vitamin B-12 have been reported as contributing to poorer cognitive function in LBC1921 at age 79, after adjusting for childhood intelligence. Because incident dementia was not previously ascertained within LBC1921, it is possible that preclinical or unrecognized cases at age 79 influenced findings. Dementia cases arising over approximately 16 years of follow-up were determined by a consensus using evidence from electronic medical records, death certificates, and clinical reviews. The analyses from the original reports were repeated after the exclusion of those who had developed dementia. In a subsequent set of analyses, the authors considered the potential impact of terminal decline, excluding those participants who died within 4 years of baseline testing. Positive APOE ε4 status was found to be associated with poorer Logical Memory (Wechsler, 1987) at age 79 (F(1, 355) = 8.16, p = .005, ηp2 = 0.022; n = 359) and lower Moray House Test (Scottish Council for Research in Education, 1933) score at age 79 (F(1, 357) = 4.27, p = .04, ηp2 = 0.012; n = 363). Lower age 79 IQ was associated with smoking (F(2, 360) = 3.67, p = .026, ηp2 = 0.020; n = 367), lower vitamin B-12 (Sβ = 0.11, p = .014; n = 367), and poorer physical fitness (Sβ = 0.21, p < .001; n = 359). Only the relationship with physical fitness remained significant after excluding those who died within 4 years of baseline (Sβ = 0.203, p < .001; n = 310). Unrecognized dementia had little or no effect on determinants of lifetime cognitive ageing in LBC1921. Terminal decline may have accounted for the associations with age 11 to age 79 cognitive change. (PsycINFO Database Record
| S-EPMC6001941 | biostudies-literature
Project description:IntroductionWe test whether measures of the retinal vasculature are associated with cognitive functioning and cognitive change.MethodsRetinal images from a narrow-age cohort were analyzed using Vessel Assessment and Measurement Platform for Images of the Retina, producing a comprehensive range of quantitative measurements of the retinal vasculature, at mean age 72.5 years (SD = 0.7). Cognitive ability and change were measured using a battery of multiple measures of memory, visuospatial, processing speed, and crystallized cognitive abilities at mean ages 73, 76, and 79 years. We applied multivariate growth curve models to test the association between retinal vascular measurements with cognitive abilities and their changes.ResultsAlmost all associations were nonsignificant. In our most parsimonious model, venular asymmetry factor was associated with speed at age 73.DiscussionOur null findings suggest that the quantitative retinal parameters applied in this study are not significantly associated with cognitive functioning or cognitive change.
| S-EPMC6625967 | biostudies-literature
Project description:OBJECTIVE:To investigate whether people with more positive attitudes to ageing are biologically younger as defined by leucocyte telomere length, accelerated DNA methylation GrimAge (AgeAccelGrim) and brain-predicted age difference, and whether these biomarkers explain relationships between attitudes to ageing and mortality. METHODS:We used linear regression to examine cross-sectionally attitudes to ageing (measured using the Attitudes to Ageing Questionnaire) and the three biomarkers in 758 adults, mean age 72.5 years, from the Lothian Birth Cohort 1936. We used Cox proportional hazards models to examine longitudinally attitudes to ageing and mortality and the role of the biomarkers. RESULTS:More positive attitude to physical change was associated with younger biological age, as measured by AgeAccelGrim and brain-predicted age difference in age-adjusted and sex-adjusted models: for an SD higher score, AgeAccelGrim was lower by -0.73 (95% CI -1.03 to -0.42) of a year, and brain-predicted age difference was lower by -0.87 (1.51 to 0.23) of a year. Both associations were attenuated by adjustment for covariates and not significant after simultaneous adjustment for all covariates and correction for multiple testing. More positive attitudes to physical change were associated with lower mortality: for an SD higher score the age-adjusted and sex-adjusted HR (95%?CI) was 0.66 (0.56 to 0.78). Adjustment for AgeAccelGrim or brain-predicted age difference attenuated this association slightly. It remained significant after adjustment for all covariates. CONCLUSION:We found partial evidence that attitudes to ageing are linked with ageing biomarkers but they accounted for only a little of the association between attitudes and mortality.
| S-EPMC7079194 | biostudies-literature
Project description:BackgroundThe ageing process is characterized by declines in physical and cognitive function. However, the relationship between these trajectories remains a topic of investigation.MethodsUsing four data waves collected triennially between ages 70 and 79, we tested for associations between multiple cognitive ability domains (verbal memory, processing speed, and visuospatial ability) and physical functions (walking speed, grip strength, and lung function). We first tested for associations between linear declines in physical and cognitive functions over the entire 9-year study period, and then, for lead-lag coupling effects between 3-year changes in cognitive and physical functions.ResultsSteeper linear decline in walking speed was moderately correlated with steeper linear declines in each cognitive domain. Steeper linear decline in grip strength was moderately correlated with steeper linear declines in verbal memory and processing speed. Lead-lag coupling models showed that decline in verbal memory was preceded by declines in walking speed and grip strength. By contrast, decline in grip strength was preceded by declines in processing speed and visuospatial ability, and decline in walking speed was preceded by decline in visuospatial ability. Following additional adjustment for covariates, only coupling effects from earlier decline in processing speed to later decline in grip strength remained significant (β = 0.545, p = .006).ConclusionOur findings provide further evidence of an association between cognitive and physical declines and point to the potential order in which these changes occur. Decline in processing speed in particular may serve as a unique early marker of declining upper body strength.
| S-EPMC7447860 | biostudies-literature
Project description:ObjectivesLoneliness 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.MethodWe 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.ResultsBetter 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.DiscussionOur 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.
| S-EPMC6777773 | biostudies-literature