{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:59:29Z","timestamp":1780606769864,"version":"3.54.1"},"reference-count":36,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T00:00:00Z","timestamp":1486684800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2017,3,4]]},"abstract":"<jats:p>Stratification by genetic risk factors for Alzheimer\u2019s disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60\u201370 years (subset n\u200a=\u200a3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500\u200akb distance of the APOE locus. Additive and multiplicative effects of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta \u20130.04, p\u200a=\u200a0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes ( p\u200a=\u200a0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5% of the distribution) show cognitive decrements, albeit much smaller than for APOE \u025b4 \u025b4 compared to \u025b3 \u025b3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD.<\/jats:p>","DOI":"10.3233\/jad-161070","type":"journal-article","created":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T09:46:10Z","timestamp":1486719970000},"page":"275-283","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["Genetic Stratification to Identify Risk Groups for Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"57","author":[{"given":"Riccardo E.","family":"Marioni","sequence":"first","affiliation":[{"name":"Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK"},{"name":"Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK"},{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 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