A comparison of parametric models for the investigation of the shape of cognitive change in the older population.

BACKGROUND: Cognitive decline is a major threat to well being in later life. Change scores and regression based models have often been used for its investigation. Most methods used to describe cognitive decline assume individuals lose their cognitive abilities at a constant rate with time. The investigation of the parametric curve that best describes the process has been prevented by restrictions imposed by study design limitations and methodological considerations. We propose a comparison of parametric shapes that could be considered to describe the process of cognitive decline in late life. Attrition plays a key role in the generation of missing observations in longitudinal studies of older persons. As ignoring missing observations will produce biased results and previous studies point to the important effect of the last observed cognitive score on the probability of dropout, we propose modelling both mechanisms jointly to account for these two considerations in the model likelihood. METHODS: Data from four interview waves of a population based longitudinal study of the older population, the Cambridge City over 75 Cohort Study were used. Within a selection model process, latent growth models combined with a logistic regression model for the missing data mechanism were fitted. To illustrate advantages of the model proposed, a sensitivity analysis of the missing data assumptions was conducted. RESULTS: Results showed that a quadratic curve describes cognitive decline best. Significant heterogeneity between individuals about mean curve parameters was identified. At all interviews, MMSE scores before dropout were significantly lower than those who remained in the study. Individuals with good functional ability were found to be less likely to dropout, as were women and younger persons in later stages of the study. CONCLUSION: The combination of a latent growth model with a model for the missing data has permitted to make use of all available data and quantify the effect of significant predictors of dropout on the dropout and observational processes. Cognitive decline over time in older persons is often modelled as a linear process, though we have presented other parametric curves that may be considered.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Methods for handling longitudinal outcome processes truncated by dropout and death.

Cohort data are often incomplete because some subjects drop out of the study, and inverse probability weighting (IPW), multiple imputation (MI), and linear increments (LI) are methods that deal with such missing data. In cohort studies of ageing, missing data can arise from dropout or death. Methods that do not distinguish between these reasons for missingness typically provide inference about a hypothetical cohort where no one can die (immortal cohort). It has been suggested that inference about the cohort composed of those who are still alive at any time point (partly conditional inference) may be more meaningful. MI, LI, and IPW can all be adapted to provide partly conditional inference. In this article, we clarify and compare the assumptions required by these MI, LI, and IPW methods for partly conditional inference on continuous outcomes. We also propose augmented IPW estimators for making partly conditional inference. These are more efficient than IPW estimators and more robust to model misspecification. Our simulation studies show that the methods give approximately unbiased estimates of partly conditional estimands when their assumptions are met, but may be biased otherwise. We illustrate the application of the missing data methods using data from the 'Origins of Variance in the Old-old' Twin study

Pequeños concursos y quiebras

En este trabajo abordaremos la frecuente problemática del derecho concursal ocasionada por la inadecuación del tratamiento respecto del pequeño concurso y su consecuencia: la desnaturalización de las soluciones que el mismo predica, cual es el caso de los pedidos de concursos y quiebra abusivos; para proponer una solución jurisprudencial abarcativa de este segmento social. Cabe agregar que son varias las hipótesis de abuso del derecho en materia concursal. Se han señalado las siguientes tipologías de desvío de las estructuras procedimentales concursales: 3 a) Abuso del procedimiento en caso de pedido de quiebra necesaria. b) Abuso del procedimiento en el caso de quiebra voluntaria. c) Abuso del procedimiento en el caso del deudor que solicita su propio concursamiento. d) Abuso del proceso en los pedidos de conversión de quiebra en concurso preventivo. Los últimos tres casos son protagonizados por deudores que buscan paralizar subastas inminentes, a tenor del efecto que produce tanto el concurso preventivo como la quiebra de suspender los "actos de ejecución forzada".Fil: García, María Carolina. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Terrera, Paula Andrea. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Education, occupational class, and cognitive decline in preclinical dementia

We investigated education and occupational influences as markers of cognitive reserve in relation to cognitive performance and decline on multiple fluid and crystallized abilities in preclinical dementia. From the total sample of 702 participants stemming from the OCTO-Twin Study (Sweden), aged 80+ at baseline in 1992-1993, only those who developed dementia during the study period (N = 127) were included in these analyses. Random effects models were used to examine the level of performance at the time of dementia diagnosis and the rates of decline prior to diagnosis. The results demonstrated that both fluid and crystallized abilities decline in preclinical stages, and that education and occupational class have independent moderating roles on the cognitive performance at the time of diagnosis, but not on the rates of decline

An international evaluation of cognitive reserve and memory changes in early old age in ten European countries

BACKGROUND: Cognitive reserve was postulated to explain individual differences in susceptibility to ageing, offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age. METHODS: Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe (SHARE), were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models (LGM). Education was used as a marker of cognitive reserve and evaluated in associations with memory performance and rate of change, while accounting for income, general health, smoking, body mass index (BMI), sex and baseline age. RESULTS: In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 (SE=0.003) & 0.006 (SE=0.002), and Switzerland for immediate recall 0.006 (SE=0.003). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 (SE=0.003)). CONCLUSIONS: We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment

Coordinated analysis of age, sex, and education effects on change in MMSE scores

Objectives. We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline.Method. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point.Results. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time.Conclusion. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. © 2012 The Author

Population sampling in longitudinal suverys

The paper questions the need for observational studies to achieve representativeness for real populations, in particular for longitudinal studies. It draws upon recent debates and argues for the need to distinguish scientific inference from population inference

Does education explain the terminal decline in the oldest-old? Evidence from two longitudinal studies of ageing

AbstractBackground Cognitive performance substantially deteriorates close to death, as postulated by the terminal decline hypothesis. However, the association between education and terminal decline remains controversial. This study investigated the role of education in terminal decline in two European longitudinal studies of oldest-old. Methods Participants were from the Newcastle 85+, UK (n=702), and Octogenarian Twins (OCTO-Twin), Sweden (n= 845). They were assessed biannually over three and five consecutive waves, respectively. In a coordinated analysis, multilevel models were used to examine the association between education and terminal decline on mini-mental state examination (MMSE), controlling for age at baseline, dementia incidence, sex, and time to death from the study entry within each cohort. Cognitive decline was modelled as a linear function of time to death in both cohorts and as a quadratic function in the OCTO-Twin study (because of longer follow-up). Education was a continuous measure (ranging from 6 to 20 years in Newcastle 85+ and 0 to 23 years in OCTO-Twin). Findings A typical British man, aged 85 at baseline, with 10 years’ education, entered the terminal phase at around 2·5 years before death, and the mean rate of decline was −1·04 MMSE points with each year closer to the time of death (SEM 0·25, p<0·0001). By contrast, a Swedish man, aged 83 years, with an average of 7 years’ education, entered the terminal phase at around 8 years from death, after which the rate of cognitive decline steepened by −1·70 points per year closer to the time of death (SEM 0·20, p<0·0001) and accelerated by −0·11 (SEM 0·01, p<0·0001). Education was positively associated with the estimated mean MMSE scores before death only in OCTO-Twin (0·43, SEM 0·15; p=0·003) and did not attenuate the rate of terminal decline in either cohort. Interpretation Decline and acceleration of this decline were detectable in both studies before death, with steeper rates of decline observed in the Swedish cohort. However, this process was not lessened by education itself. This work contributes to a better understanding of the transition from the subtle cognitive changes associated with age to those of neurological substance, and the role of education in this decline. Funding The funding sources of this work were the Alzheimer's Society (grant number 144) and the Medical Research Council (unit programme number MC_UU_12019/1)

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

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 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