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Objective The objective of this study was to examine practice effects and longitudinal cognitive change in 190 clinically normal elderly classified according to a two-feature biomarker model for Alzheimer's disease. Methods All participants completed neuropsychological testing, MRI, FDG-PET and PiB-PET at their baseline evaluation. We divided participants into four groups based on neuroimaging measures of amyloid (A+ or A-) and neurodegeneration (N+ or N-) and reexamined cognition at 15- and 30-month intervals. Results The A-N- group showed significant improvements in the memory and global scores. The A+N- group also showed significant improvements in the memory and global scores as well as attention. The A-N+ group showed a significant decline in attention at 30 months. The A+N+ group showed significant improvements in memory and the global score at 15 months followed by a significant decline in the global score at 30 months. Conclusion Amyloidosis in the absence of neurodegeneration did not have an adverse impact on practice effects or the 30-month cognitive trajectories. In contrast, participants with neurodegeneration (either A-N+ or A+N+) had worse performance at the 30-month follow-up. Our results show that neurodegeneration has a more deleterious effect on cognition than amyloidosis in clinically normal individuals.

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