Longitudinal cognitive decline in the AIBL cohort: The role of APOE ε4 status

The epsilon 4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the epsilon 4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the epsilon 4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE epsilon 4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired individuals enroled in the AIBL Study of Ageing. We compared individuals within each group with and without an epsilon 4 allele. Healthy Controls with an epsilon 4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired individuals with an epsilon 4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of epsilon 4-related cognitive ageing. (C) 2015 Elsevier Ltd. All rights reserved.