Sample size and classification error for Bayesian change-point models with unlabelled sub-groups and incomplete follow-up

Many medical (and ecological) processes involve the change of shape, whereby one trajectory changes into another trajectory at a specific time point. There has been little investigation into the study design needed to investigate these models. We consider the class of fixed effect change-point models with an underlying shape comprised two joined linear segments, also known as broken-stick models. We extend this model to include two sub-groups with different trajectories at the change-point, a change and no change class, and also include a missingness model to account for individuals with incomplete follow-up. Through a simulation study, we consider the relationship of sample size to the estimates of the underlying shape, the existence of a change-point, and the classification-error of sub-group labels. We use a Bayesian framework to account for the missing labels, and the analysis of each simulation is performed using standard Markov chain Monte Carlo techniques. Our simulation study is inspired by cognitive decline as measured by the Mini-Mental State Examination, where our extended model is appropriate due to the commonly observed mixture of individuals within studies who do or do not exhibit accelerated decline. We find that even for studies of modest size ( n = 500, with 50 individuals observed past the change-point) in the fixed effect setting, a change-point can be detected and reliably estimated across a range of observation-errors. </jats:p

Dynamic Longitudinal Associations Between Social Support and Cognitive Function: A Prospective Investigation of the Directionality of Associations

OBJECTIVE: To investigate the reciprocity of social support and cognitive function in late life. METHOD: Analyses were based on three parallel repeat measures of social support and cognition from the Whitehall II cohort, providing 10-year follow-up of 6,863 participants (mean age 55.8 years, SD 6.0 at baseline). Alternative hypotheses were evaluated via four bivariate dual change score models: Full coupling model estimated mutual influences of social support and cognition on subsequent changes in each other; social causation model assumed a unidirectional influence from social support onto changes in cognition, while the opposite assumption was tested by health selection model; last, no coupling model suggested independent growth of these two sets of variables. RESULTS: A better cognition at the preceding stage was related to less positive changes in confiding support and less negative changes in practical support. In contrast, influences from social support on subsequent changes in cognition were not detected. DISCUSSION: This empirical study provides some evidence for the health selection mechanism, such that cognition modified changes in social support. The hypothesized neuroprotective effect of social support was not detectable

The long arm of childhood intelligence on terminal decline:Evidence from the Lothian Birth Cohort 1921

The current study investigates the heterogeneity of cognitive trajectories at the end of life by assigning individuals into groups according to their cognitive trajectories prior to death. It also examines the role of childhood intelligence and education on these trajectories and group membership. Participants were drawn from the Lothian Birth Cohort of 1921 (LBC1921), a longitudinal study of individuals with a mean age of 79 years at study entry, and observed up to a maximum of five times to their early 90s. Growth mixture modelling was employed to identify groups of individuals with similar trajectories of global cognitive function measured with the Mini-Mental State Examination (MMSE) in relation to time to death, accounting for childhood intelligence, education, the time to death from study entry, and health conditions (hypertension, diabetes and cardiovascular disease). Two distinct groups of individuals (classes) were identified: a smaller class (18% of the sample) of individuals whose MMSE scores dropped linearly with about 0.5 MMSE points per year closer to death, and a larger group (82% of the sample) with stable MMSE across the study period. Only childhood intelligence was found to be associated with an increased probability of belonging to the stable class of cognitive functioning prior to death (odds ratio=1.08, standard error=0.02, p≤.001). These findings support a protective role of childhood intelligence, a marker of cognitive reserve, against the loss of cognitive function prior to death. Our results also suggest that terminal decline is not necessarily a normative process

Association between anticholinergic burden and dementia in UK Biobank

Abstract Background Previous studies on the relationship between anticholinergic drugs and dementia have reported heterogeneous results. This variability could be due to different anticholinergic scales and differential effects of distinct classes of drugs. Methods Using Cox proportional hazards models, we computed the association between annual anticholinergic burden (AChB) and the risk of dementia in UK Biobank with linked general practitioner prescription records between the years 2000 and 2015 (n = 171,775). Results AChB according to most anticholinergic scales (standardized odds ratio range: 1.027–1.125) and the slope of the AChB trajectory (hazard ratio = 1.094; 95% confidence interval: 1.068–1.119) were predictive of dementia. However, the association between AChB and dementia held only for some classes of drugs, especially antidepressants, antiepileptics, and antidiuretics. Discussion The heterogeneity in previous findings may partially be due to different effects for different classes of drugs. Future studies should establish differences in more detail and further examine the practicality of a general measure of AChB relating to the risk of dementia

Co-occurrence and clustering of health conditions at age 11: cross-sectional findings from the Millennium Cohort Study

OBJECTIVES: To identify patterns of co-occurrence and clustering of 6 common adverse health conditions in 11-year-old children and explore differences by sociodemographic factors. DESIGN: Nationally representative prospective cohort study. SETTING: Children born in the UK between 2000 and 2002. PARTICIPANTS: 11 399 11-year-old singleton children for whom data on all 6 health conditions and sociodemographic information were available (complete cases). MAIN OUTCOME MEASURES: Prevalence, co-occurrence and clustering of 6 common health conditions: wheeze; eczema; long-standing illness (excluding wheeze and eczema); injury; socioemotional difficulties (measured using Strengths and Difficulties Questionnaire) and unfavourable weight (thin/overweight/obese vs normal). RESULTS: 42.4% of children had 2 or more adverse health conditions (co-occurrence). Co-occurrence was more common in boys and children from lower income households. Latent class analysis identified 6 classes: 'normative' (57.4%): 'atopic burdened' (14.0%); 'socioemotional burdened' (11.0%); 'unfavourable weight/injury' (7.7%); 'eczema/injury' (6.0%) and 'eczema/unfavourable weight' (3.9%). As with co-occurrence, class membership differed by sociodemographic factors: boys, children of mothers with lower educational attainment and children from lower income households were more likely to be in the 'socioemotional burdened' class. Children of mothers with higher educational attainment were more likely to be in the 'normative' and 'eczema/unfavourable weight' classes. CONCLUSIONS: Co-occurrence of adverse health conditions at age 11 is common and is associated with adverse socioeconomic circumstances. Holistic, child focused care, particularly in boys and those in lower income groups, may help to prevent and reduce co-occurrence in later childhood and adolescence

Education associated with a delayed onset of terminal decline

Background: the terminal decline hypothesis suggests an acceleration in the rate of loss of cognitive function before death. Evidence about the association of educational attainment and the onset of terminal decline is scarce. Objective: to investigate the association of education with the onset of terminal decline in global cognitive function measured by Mini Mental State Exam (MMSE) scores. Subjects: deceased participants of the Cambridge City over 75 Cohort Study who were interviewed at about 2, 7, 9, 13, 17 and 21 years after baseline. Methods: regular and Tobit random change point growth models were fitted to MMSE scores to identify the onset of terminal decline and assess the effect of education on this onset. Results: people who left school at an older age had a delayed onset of terminal decline. Thus better educated individuals experience a slightly shorter period of faster decline before death. Conclusion: an important finding emerging from our work is that education does appear to delay the onset of terminal decline, although only by a limited amount