Differential Cognitive Decline in Alzheimer's Disease Is Predicted by Changes in Ventricular Size but Moderated by Apolipoprotein E and Pulse Pressure

Background: Differential cognitive trajectories in Alzheimer's disease (AD) may be predicted by biomarkers from multiple domains. Objective: In a longitudinal sample of AD and AD-related dementias patients (n = 312), we tested whether 1) change in brain morphometry (ventricular enlargement) predicts differential cognitive trajectories, 2) further risk is contributed by genetic (Apolipoprotein E [APOE] epsilon 4+) and vascular (pulse pressure [PP]) factors separately, and 3) the genetic + vascular risk moderates this pattern. Methods: We applied a dynamic computational approach (parallel process models) to test both concurrent and change-related associations between predictor (ventricular size) and cognition (executive function [EF]/attention). We then tested these associations as stratified by APOE (epsilon 4-/epsilon 4+), PP (low/high), and APOE+ PP (low/intermediate/high) risk. Results: First, concurrently, higher ventricular size predicted lower EF/attention performance and, longitudinally, increasing ventricular size predicted steeper EF/attention decline. Second, concurrently, higher ventricular size predicted lower EF/attention performance selectively in APOE epsilon 4+ carriers, and longitudinally, increasing ventricular size predicted steeper EF/attention decline selectively in the low PP group. Third, ventricular size and EF/attention associations were absent in the high APOE+ PP risk group both concurrently and longitudinally. Conclusion: As AD progresses, a threshold effect may be present in which ventricular enlargement in the context of exacerbated APOE+ PP risk does not produce further cognitive decline.

Automated summary

This study aimed to explore cognitive trajectories in Alzheimer's disease patients, finding that changes in ventricular size can predict cognitive trajectories, while APOE and PP risk factors can influence this pattern; additionally, as AD progresses, ventricular enlargement in the context of heightened APOE + PP risk may no longer lead to further cognitive decline.