Cognition-Mortality Associations Are More Pronounced When Estimated Jointly in Longitudinal and Time-to-Event Models

Abstract

With aging populations worldwide, there is growing interest in links between cognitive decline and elevated mortality risk—and, by extension, analytic approaches to further clarify these associations. Toward this end, some researchers have compared cognitive trajectories of survivors vs. decedents while others have examined longitudinal changes in cognition as predictive of mortality risk. A two-stage modeling framework is typically used in this latter approach; however, several recent studies have used joint longitudinal-survival modeling (i.e., estimating longitudinal change in cognition conditionally on mortality risk, and vice versa). Methodological differences inherent to these approaches may influence estimates of cognitive decline and cognition-mortality associations. These effects may vary across cognitive domains insofar as changes in broad fluid and crystallized abilities are differentially sensitive to aging and mortality risk. We compared these analytic approaches as applied to data from a large-sample, repeated-measures study of older adults (N = 5,954; ages 50–87 years at assessment; 4,453 deceased at last census). Cognitive trajectories indicated worse performance in decedents and when estimated jointly with mortality risk, but this was attenuated after adjustment for health-related covariates. Better cognitive performance predicted lower mortality risk, and, importantly, cognition-mortality associations were more pronounced when estimated in joint models. Associations between mortality risk and crystallized abilities only emerged under joint estimation. This may have important implications for cognitive reserve, which posits that knowledge and skills considered well-preserved in later life (i.e., crystallized abilities) may compensate for declines in abilities more prone to neurodegeneration, such as recall memory and problem solving. Joint longitudinal-survival models thus appear to be important (and currently underutilized) for research in cognitive epidemiology.

Movement Disorders and Mortality in Severely Mentally Ill Patients: The Curacao Extrapyramidal Syndromes Study XIV

“…In contrast, other factors, i.e. symptom severity, 44 cognitive functioning, [38][39][40]50 physical activity, 41 use of alcohol, illicit drug use, 51 and smoking 52 have been found to be related to both MD and mortality and the lack of information on those variables puts a limitation to the present findings.…”

Orientation Experiences and Navigation Aid Use: A Self-Report Lifespan Study on the Role of Age and Visuospatial Factors

“…This result could reflect that people who go out more and are active in finding their way are inevitably more exposed to potentially negative experiences in the environment, such as getting lost. Taken together, the result for years of education implies the need to promote lifelong learning, even in older age [66], to sustain spatial behaviors and thus navigation in the environment, which, in turn, promotes active aging. Regarding the role of gender, females reported going out less and not using navigation aids, such as maps and GPS, preferring the use of verbal directions.…”

Joint Longitudinal and Survival Models to Study Vulnerability Processes

“…Regarding cognitive abilities, levels of and/or rate of change in memory, processing speed, or verbal fluency also predicted both risk of dying and/or being diagnosed with Alzheimer's disease (Ghisletta, 2008;Ghisletta et al, 2006;McArdle et al, 2005;Muniz-Terrera et al, 2011). Moreover, Aichele et al (2021) compared direct predictions from a JM to those of a two-step estimation procedure and showed that JM has greater power to estimate associations between cognitive decline and mortality in a large sample of adults. Based on these encouraging results in the health and cognitive literature, we therefore advocate that researchers consider JM a promising statistical tool to further the understanding of vulnerability processes throughout the life course.…”