Evaluating the 8-Year Association Between Cognition and Beta Amyloid in the Dallas Lifespan Brain Study Cohort

Mounting evidence suggests beta amyloid (Aβ) is not the sole initiating driver of cognitive decline in Alzheimer's disease (AD). This study explores whether there is an association between cognitive decline over eight years and Aβ.

Data from 48 participants in the Dallas Lifespan Brain Study (DLBS) were analyzed in the present study. Prior to selection, participants were classified as Aβ⁺ or Aβ^- based on global Aβ deposition. All 24 Aβ⁺ participants with complete data for the purposes of the present study were sex- and age-matched with an Aβ^- participant and assorted into two respective Aβ groups. Cognitive decline across episodic memory, working memory, processing speed, and reasoning was then compared between the two groups over an 8-year observation period.

An association between cognitive decline over 8 years and the Aβ group was observed in reasoning but not across episodic memory, working memory, and processing speed. Still, there were differences between the two groups that reached significance on an episodic memory task (p = 0.035) and trended toward significance on an encompassing episodic memory composite (p = 0.057). Post-hoc comparisons revealed these differences were only significant at epoch 1. Broad declines in cognition were also found over the observation period, irrespective of Aβ group.

Our results contribute to the mounting evidence that suggests Aβ is not the sole initiating driver of cognitive decline in AD. However, the present study has limitations, including a relatively small sample size that must be accounted for when considering the null findings to prevent overinterpretation. Future work should validate our results in larger, similarly controlled samples and model additional AD biomarkers and risk factors to explore different mechanisms for cognitive decline in AD.