Abstract
Background
Genetic variation in Spondin-1 (SPON1), specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. The aim of this study was to assess whether the association was present in cognitively normal (CN) older adults.
Methods
Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 CN older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study.
Results
No independent effect of rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between APOE ε4 and rs11023139 in individuals with high Aβ-amyloid burden. APOE ε4/rs11023139-A carriers declined significantly faster than APOE ε4/rs11023139-G_G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020).
Conclusions
These results suggest that carriage of the SPON1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ε4 CN older adults with a high neocortical Aβ-amyloid burden.