Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.
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van der Lee Sven J, Teunissen Charlotte E, Pool René, Shipley Martin J, Teumer Alexander, Chouraki Vincent, Melo van Lent Debora, Tynkkynen Juho, Fischer Krista, Hernesniemi Jussi, Haller Toomas, Singh-Manoux Archana, Verhoeven Aswin, Willemsen Gonneke, de Leeuw Francisca A, Wagner Holger, van Dongen Jenny, Hertel Johannes, Budde Kathrin, Willems van Dijk Ko, Weinhold Leonie, Ikram M Arfan, Pietzner Maik, Perola Markus, Wagner Michael, Friedrich Nele, Slagboom P Eline, Scheltens Philip, Yang Qiong, Gertzen Robert E, Egert Sarah, Li Shuo, Hankemeier Thomas, van Beijsterveldt Catharina E M, Vasan Ramachandran S, Maier Wolfgang, Peeters Carel F W, Jörgen Grabe Hans, Ramirez Alfredo, Seshadri Sudha, Metspalu Andres, Kivimäki Mika, Salomaa Veikko, Demirkan Ayşe, Boomsma Dorret I, van der Flier Wiesje M, Amin Najaf, van Duijn Cornelia M
Аннотация
METHODS: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined.
RESULTS: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors.
DISCUSSION: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.