Abstract
Background
In non-demented adults, both high amyloid (Aβ+) and carriage of the apolipoprotein E (APOE) ε4 allele increase risk for cognitive decline and dementia. Further, Aβ+ related cognitive decline is increased substantially by the presence of at least one copy of the APOE ε4 allele. Despite advances in Aβ biomarkers, age remains the greatest risk factor for dementia, particularly Alzheimer’s disease (AD). As APOE ε4 increases risk for Aβ+ and older adults are also more likely to be Aβ+, it is important to understand the extent to which age influences the effects of ε4 on Aβ+ related memory decline. This study aimed to determine the extent to which the APOE ε4 allele influenced Aβ related cognitive change in adults aged between 60-74 and 75-90 years old.
Methods
Non-demented adults (n=485) enrolled in the AIBL study underwent Aβ neuroimaging and ε4 genotyping. Episodic Memory was assessed at baseline, 18-, 36-, 54- and 72-month follow-ups. Participants were classified as Aβ- or Aβ+ using PET neuroimaging and into two age groups (<75 and ≥75) according to their age at baseline. Data were analysed using linear mixed model analyses.
Results
In adults aged <75, when compared to the Aβ- group, there was a significant rate of memory decline only in Aβ+ ε4 carriers (d=1.25). In adults aged ≥75, when compared to the Aβ- group, both Aβ+ ε4 carriers (d=1.23) and non-carriers (d=0.35) showed significant rates of memory; however, the memory decline in Aβ+ ε4 carriers was substantially greater when compared to non-carriers (d=0.82). This faster rate of memory decline in adults aged ≥75 was reflected in a 43% of Aβ+ ε4 carriers meeting clinical criteria for dementia at the 72-month assessment, in contrast to just 24% of Aβ+ ε4 non-carriers and 10% of Aβ- participants.
Conclusions
Previous studies investigating the relationship between ε4 and Aβ+ have not accounted for potential non-linear effects of age on memory decline. The rate of Aβ+ related memory decline was greatest in adults aged ≥75, particularly in those who were also APOE ε4 carriers. This suggests that the combined effects of Aβ+ and ε4 on risk for dementia increases substantially in older adults.