Association of genetic risk factors with cognitive decline: the PATH through life project

We examined the association of 28 single nucleotide polymorphisms (SNPs), previously associated with dementia or cognitive performance, with tests assessing episodic memory, working memory, vocabulary, and perceptual speed in 1689 nondemented older Australians of European ancestry. In addition to testing each variant individually, we assessed the collective association of the 12-risk SNPs for late-onset Alzheimer's disease using weighted and unweighted genetic risk scores. Significant associations with cognitive performance were observed for APOE ε4 allele, ABCA7-rs3764650, CR1-rs3818361, MS4A4E-rs6109332, BDNF-rs6265, COMT-rs4680, CTNNBL-rs6125962, FRMD4A-rs17314229, FRMD4A-rs17314229, intergenic SNP chrX-rs12007229, PDE7A-rs10808746, SORL1-rs668387, and ZNF224-rs3746319. In addition, the weighted genetic risk score was associated with worse performance on episodic memory. The identification of genetic risk factors, that act individually or collectively, may help in screening for people with elevated risk of cognitive decline and for understanding the biological pathways that underlie cognitive decline.