RESUMEN
. BACKGROUND: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. OBJECTIVE: The aim of this study was to assess whether the association was present in cognitively normal older adults. METHODS: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. RESULTS: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) É4 and rs11023139 in individuals with high amyloid-ß burden. APOE É4/rs11023139-A carriers declined significantly faster than APOE É4/rs11023139-G_G carriers in measures of global cognition (pâ=â0.011) and verbal episodic memory (pâ=â0.020). CONCLUSION: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE É4 cognitively normal older adults with a high neocortical amyloid-ß burden.