Patterns of multi-domain cognitive aging in participants of the Long Life Family Study

Maintaining good cognitive function at older age is important, but our knowledge of patterns and predictors of cognitive aging is still limited. We used Bayesian model-based clustering to group 5064 participants of the Long Life Family Study (ages 49-110 years) into clusters characterized by distinct trajectories of cognitive change in the domains of episodic memory, attention, processing speed, and verbal fluency. For each domain, we identified 4 or 5 large clusters with representative patterns of change ranging from rapid decline to exceptionally slow change. We annotated the clusters by their correlation with genetic and molecular biomarkers, non-genetic risk factors, medical history, and other markers of aging to discover correlates of cognitive changes and neuroprotection. The annotation analysis discovered both predictors of multi-domain cognitive change such as gait speed and predictors of domain-specific cognitive change such as IL6 and NTproBNP that correlate only with change of processing speed or APOE genotypes that correlate only with change of processing speed and logical memory. These patterns also suggest that cognitive decline starts at young age and that maintaining good physical function correlates with slower cognitive decline. To better understand the agreement of cognitive changes across multiple domains, we summarized the results of the cluster analysis into a score of cognitive function change. This score showed that extreme patterns of change affecting multiple cognitive domains simultaneously are rare in this study and that specific signatures of biomarkers of inflammation and metabolic disease predict severity of cognitive changes. The substantial heterogeneity of change patterns within and between cognitive domains and the net of correlations between patterns of cognitive aging and other aging traits emphasizes the importance of measuring a wide range of cognitive functions and the need for studying cognitive aging in concert with other aging traits.