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• W4381052428 endingPage "100081" @default.
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• W4381052428 abstract "The cause of the most common form of dementia, sporadic Alzheimer's disease (AD), remains unknown. This may reflect insufficiently powered studies to date for this multi-factorial disorder. The UK Biobank dataset presents a unique opportunity to rank known risk factors and determine novel variables.A custom machine learning approach for high dimensionality data was applied to explore prospectively associations between AD in a sub-cohort of 156,209 UK Biobank participants aged 60-70 including more than 2,090 who were subsequently diagnosed with AD.After the possession of the APOE4 allele, the next highest ranked risk factors were other genetic variants within the TOMM40-APOE-APOC1 locus. When stratified by their apolipoprotein epsilon 4 (APOE4) carrier status, the most prominent risk factors in carriers were AST:ALT ratio, the number of treatments/ medications taken as well as time spent in hospital while protection was conferred by Sleeplessness/Insomnia. In non-APOE carriers, lower socioeconomic status and fewer years of education were highly ranked but effect sizes were small relative to APOE4 carriers.Possession of the APOE4 allele was confirmed as the most important risk factor in AD. Other TOMM40-APOE-APOC1 locus variants further moderate the risk of AD in APOE4 carriers. Liver pathology is a novel risk factor in APOE4 carriers while Sleeplessness/Insomnia is protective in AD irrespective of APOE4 status. Other factors such as Number of treatments/ medications suggest that multimorbidity is an important risk factor for AD. Future treatments aimed at co-morbidities, including liver disease, may concomitantly lower the risk of sporadic AD." @default.
• W4381052428 created "2023-06-18" @default.
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• W4381052428 date "2023-01-01" @default.
• W4381052428 modified "2023-10-18" @default.
• W4381052428 title "Ranking the risk factors for Alzheimer’s disease; findings from the UK Biobank study" @default.
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• W4381052428 doi "https://doi.org/10.1016/j.nbas.2023.100081" @default.
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