The Latent Factor Structure Underlying Regional Brain Volume Change and Its Relation to Cognitive Change in Older Adults

Objective: Late-life changes in cognition and brain integrity are both highly multivariate, time-dependent processes that are essential for understanding cognitive aging and neurodegenerative disease outcomes. The present study seeks to identify a latent variable model capable of efficiently reducing a multitude of structural brain change magnetic resonance imaging (MRI) measurements into a smaller number of dimensions. We further seek to demonstrate the validity of this model by evaluating its ability to reproduce patterns of coordinated brain volume change and to explain the rate of cognitive decline over time. Method: We used longitudinal cognitive data and structural MRI scans, obtained from a diverse sample of 358 participants (Mage = 74.81, SD = 7.17), to implement latent variable models for measuring brain change and to estimate the effects of these brain change factors on cognitive decline. Results: Results supported a bifactor model for brain change with four group factors (prefrontal, temporolimbic, medial temporal, and posterior association) and one general change factor (global atrophy). Atrophy in the global (β = 0.434, SE = 0.070), temporolimbic (β = 0.275, SE = 0.085), and medial temporal (β = 0.240, SE = 0.085) factors were the strongest predictors of global cognitive decline. Overall, the brain change model explained 59% of the variance in global cognitive slope. Conclusions: The current results suggest that brain change across 27 bilateral regions of interest can be grouped into five change factors, three of which (global gray matter, temporolimbic, and medial temporal lobe atrophy) are strongly associated with cognitive decline. Key Points Question: Are there patterns of coordinated regional brain changes that underlie aging-associated changes in cognitive functioning? Findings: In addition to global brain atrophy, four specific factors underlying regional brain atrophy (corresponding to volume changes in prefrontal association cortex, posterior association cortex, temporolimbic areas, and medial temporal lobes) are dissociable from one another; three of these (global, temporolimbic, and medial temporal) exert a strong influence over global cognitive decline. Importance: These findings allow us to reduce dozens of brain volume measurements into a smaller number of elements that (a) represent systematic patterns of change in cortical ROI volumes and (b) explain 59% of the variance in aging-associated cognitive decline. Next Steps: The ide