title: Late Onset Alzheimer's Disease Risk Variants in Cognitive Decline: The PATH Through Life Study.
abstract: Recent genome wide association studies have identified a number of single nucleotide polymorphisms associated with late onset Alzheimer's disease (LOAD). We examined the associations of 24 LOAD risk loci, individually and collectively as a genetic risk score, with cognitive function. We used data from 1,626 non-demented older Australians of European ancestry who were examined up to four times over 12 years on tests assessing episodic memory, working memory, vocabulary, and information processing speed. Linear mixed models were generated to examine associations between genetic factors and cognitive performance. Twelve SNPs were significantly associated with baseline cognitive performance (ABCA7, MS4A4E, SORL1), linear rate of change (APOE, ABCA7, INPP5D, ZCWPW1, CELF1), or quadratic rate of change (APOE, CLU, EPHA1, HLA-DRB5, INPP5D, FERMT2). In addition, a weighted genetic risk score was associated with linear rate of change in episodic memory and information processing speed. Our results suggest that a minority of AD related SNPs may be associated with non-clinical cognitive decline. Further research is required to verify these results and to examine the effect of preclinical AD in genetic association studies of cognitive decline. The identification of LOAD risk loci associated with non-clinical cognitive performance may help in screening for individuals at greater risk of cognitive decline.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Shea J
authors.initials: SJ
authors.lastname: Andrews
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Debjani
authors.initials: D
authors.lastname: Das
authors.affiliation: Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australia.
authors.forename: Kaarin J
authors.initials: KJ
authors.lastname: Anstey
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Easteal
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D001315:Australia; D060825:Cognitive Dysfunction / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
keywords: Alzheimer’s disease; cognitive aging; genetic epidemiology; genetic risk scores; longitudinal studies; single nucleotide polymorphisms