Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study

Abstract

Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change.

Keywords: Alzheimer disease; Amyloid; Attention; Biological markers; Episodic memory; Longitudinal study.

Figure 1

Spaghetti plots of individual predicted trajectories in the attention composite over time.

Figure 2

Relationship between cognition and Aβ42 (Top Panel) and PET-PIB (Bottom Panel) at baseline assessment.

Figure 3

Relationship between attention and time in study varies as a function of baseline CSF tau. For visualization, regression lines are plotted at the lowest tertile of tau (solid line, less than 190 pg/ ml), middle tertile (dashed line) and highest tertile (dotted line, greater than 276 pg / ml).

Figure 4

Spaghetti plots of individual predicted trajectories in the episodic memory composite over time.

Figure 5

Relationship between episodic memory and time in study varies as a function of baseline CSF tau. For visualization, regression lines are plotted at the lowest tertile of tau (solid line, less than 190 pg/ ml), middle tertile (dashed line) and highest tertile (dotted line, greater than 276 pg / ml).