Cognition and beta-amyloid in preclinical Alzheimer's disease: Data from the AIBL study

The 'preclinical' phase of Alzheimer's disease is a future target for treatment, but additional research is essential to understand the relationship between beta-amyloid burden and cognition during this time. We investigated this relationship using a large sample of apparently healthy older adults (N = 177), which also enabled examination of whether the relationship differed according to age, gender, years of education, apolipoprotein E status, and the presence of subjective memory complaints. In addition to episodic memory, a range of cognitive measures (global cognition, semantic memory, visuospatial performance, and executive function) were examined. Participants were aged over 60 years with no objective cognitive impairment and came from the imaging arm of the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study of ageing. C-11-PiB PET was used to measure beta-amyloid burden and a PiB 'cut-off' level of 1.5 was used to separate participants with low PiB retention from those with high PiB retention. Thirty-three percent of participants had a PiB positive scan. PiB positive participants were 5 years older, twice as likely to carry an apolipoprotein E epsilon 4 allele, and their composite episodic memory was 0.26 SD worse than PiB negative volunteers. Linear regressions with beta-amyloid burden as a dichotomous predictor, revealed an interaction between beta-amyloid burden and gender, as well as age and education effects, in predicting episodic memory and visuospatial performance. In females, but not in males, increased beta-amyloid was related to worse episodic memory and visuospatial performance. Furthermore, an interaction between beta-amyloid burden and APOE status was found in predicting visuospatial performance, whereby there was a trend for increased beta-amyloid to relate to worse visuospatial performance for those without an APOE epsilon 4 allele. There were no other main or interaction effects of beta-amyloid on any of the other composite cognitive measures. These cross-sectional findings suggest that beta-amyloid burden does not have a large effect on cognition in this subset of apparently healthy older people. The finding of gender differences deserves further research to answer definitively the important question of gender susceptibility to adverse cognitive effects from beta-amyloid. (C) 2011 Elsevier Ltd. All rights reserved.