Absence of practice effects in preclinical Alzheimer's disease

Abstract

Objective: To describe how practice effects influence cognitive trajectories and determine if a reduction in practice effects is a potential marker of Stage-III preclinical Alzheimer's disease (AD).

Method: Participants included 263 older adults who were cognitively normal at baseline (i.e., had a Clinical Dementia Rating [CDR] of 0; Morris, 1993) and returned for an average of 9.5 annual visits. Participants completed standard tests of episodic memory, visuospatial ability, semantic memory, and executive function. Progressors (n = 66) converted to CDR > 0 with a diagnosis of symptomatic AD after a minimum of 3 visits and stable participants (n = 197) never progressed to CDR > 0. Practice effects, defined as the slope of performance across Visits 1-3, were compared between groups and used within subjects to predict risk of conversion. Change-point models that accounted for retest were contrasted with linear models that ignored retest.

Results: The stable group showed practice effects on episodic-memory measures (β = 0.14, SE = .02, p < .0001) but the progressor group did not (β = 0.03, SE = .03, p = .343). Across all participants, practice effects on episodic-memory tests were associated with a decreased risk of progression to AD as indicated by the subdistribution hazards model (SHR; Fine & Gray, 1999); SHR = .110, 95% CI [.032, .384], p = .001). Finally, use of change-point models dramatically altered rate-of-change estimates compared with models that ignored practice.

Conclusion: Our results indicate that preclinical AD is marked by a reduction in practice effects in episodic memory and that the magnitude of gain from retesting is inversely related to progression risk. Assessment of practice effects may be a face-valid indicator of Stage-III preclinical AD.

Figure 1

Plot of practice effects with LOESS curves for the episodic memory composite z-score in cognitively normal (CDR 0, n=263) participants who remained normal (“Stable”, n=197), or progressed to dementia (“Progressors”, CDR>0, n=66) after a minimum of 4 assessments. Practice effects were defined as the ordinary least squares slope of cognitive performance across the first three annual assessments, as indicated by the area within the rectangle.

Figure 2

Cumulative incidence probability of progressing to a CDR=0.5 with an AD diagnosis. The ordinary least squares slope of episodic memory composite performance across the first three visits was used to predict survival. Curves were adjusted for age, gender, education, and APOE genotype. EM = Episodic Memory composite. Participants showing clear evidence of practice effects (in blue) had the lowest risk of progression.