Marioni et al., 2015. The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Marioni, R. E., Shah, S., McRae, A. F., Ritchie, S. J., Muniz-Terrera, G., Harris, S. E., Gibson, J., Redmon, P., Cox, S.R., Pattie, A., & Corley, J. (2015). The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. International journal of epidemiology, 44(4), 1388-1396.

Year: 
2015
Status: 
complete
Abstract: 

Background: 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.

Methods: 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 predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures.

Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: −0.07 to −0.05, P range: 9.7 x 10−3 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits.

Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up.

Hoffman et al., 2011. On the confounds among retest gains and age-cohort differences in the estimation of within-person change in longitudinal studies: a simulation study

Hoffman, L., Hofer, S. M., & Sliwinski, M. J. (2011). On the confounds among retest gains and age-cohort differences in the estimation of within-person change in longitudinal studies: A simulation study. Psychology and Aging, 26(4), 778-791.

Year: 
2011
Status: 
complete
Abstract: 

Although longitudinal designs are the only way in which age changes can be directly observed, a recurrent criticism involves to what extent retest effects may downwardly bias estimates of true age-related cognitive change. Considerable attention has been given to the problem of retest effects within mixed effects models that include separate parameters for longitudinal change over time (usually specified as a function of age) and for the impact of retest (specified as a function of number of exposures). Because time (i.e., intervals between assessment) and number of exposures are highly correlated (and are perfectly correlated in equal interval designs) in most longitudinal studies, the separation of effects of within-person change from effects of retest gains is only possible given certain assumptions (e.g., age convergence). To the extent that cross-sectional and longitudinal effects of age differ, obtained estimates of aging and retest may not be informative. The current simulation study investigated the recovery of within-person change (i.e., aging) and retest effects from repeated cognitive testing as a function of number of waves, age range at baseline, and size and direction of age-cohort differences on the intercept and age slope in age-based models of change. Significant bias and Type I error rates in the estimated effects of retest were observed when these convergence assumptions were not met. These simulation results suggest that retest effects may not be distinguishable from effects of aging-related change and age-cohort differences in typical long-term traditional longitudinal designs.

Dodge et al., 2017. Cohort effects in verbal memory function and practice effects: a population-based study.

Dodge, H. H., Zhu, J., Hughes, T. F., Snitz, B. E., Chang, C. C. H., Jacobsen, E. P., & Ganguli, M. (2017). Cohort effects in verbal memory function and practice effects: a population-based study. International psychogeriatrics, 29(1), 137-148.

Year: 
2017
Status: 
complete
Abstract: 

Background: In many developed countries, cognitive functioning (as measured by neuropsychological tests) appears to be improving over time in the population at large, in parallel with the declining age-specific incidence of dementia. Here, we investigated cohort effects in the age-associated trajectories of verbal memory function in older adults. We sought to determine whether they varied by decade of birth and, if so, whether the change would be explained by increasing educational attainment.

Methods: Pooling data from two prospective US population-based studies between 1987 and 2015, we identified four birth cohorts born 1902–1911, 1912–1921, 1922–1931, and 1932–1943. Among these cohorts, we compared age-associated trajectories both of performance and of practice effects on immediate and delayed recall of a 10-item Word List. We used mixed effects models, first including birth cohorts and cohort X age interaction terms, and then controlling for education and education X age interaction.

Results: We observed significant cohort effects in performance (baseline and age-associated trajectories) in both immediate recall and delayed recall, with function improving between the earliest- and latest-born cohorts. For both tests, we also observed cohort effects on practice effects with the highest levels in the latest-born cohorts. Including education in the models did not attenuate these effects.

Conclusions: In this longitudinal population study, across four decade-long birth cohorts, there were significant improvements in test performance and practice effects in verbal memory tests, not explained by education. Whether this reflects declining disease incidence or other secular trends awaits further investigation.