title: State- and trait-dependent associations of vitamin-D with brain function during aging.
abstract: We investigated whether (1) serum levels of 25-hydroxyvitamin D [25(OH)D] and single nucleotide polymorphisms (SNPs) in the group-specific component (GC) gene-regulating serum 25(OH)D levels are associated with cognition in older individuals; and (2) whether causal relationships exist between 25(OH)D and cognition during aging. Data from 1207 participants in the Baltimore Longitudinal Study of Aging were analyzed (mean follow-up, 10.4 years) to test associations between serum 25(OH)D and cognition. Two GC SNPs were used to derive a composite genetic risk score associated with lower 25(OH)D concentrations. Lower serum 25(OH)D and higher GC composite scores were associated with lower executive function at baseline. Mendelian randomization analyses suggested a causal relationship between lower serum 25(OH)D and poorer executive function and psychomotor speed. The SNP score was also associated with lower performance on measures of visuospatial abilities at baseline but with attenuated declines over time in visuospatial abilities and executive function. Widespread associations between vitamin-D regulatory SNPs and cognition suggest a mechanistic basis for the relationship between serum 25(OH)D levels and cognition during aging.
authors.affiliation: Unit of Clinical and Translational Neuroscience, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Kueider
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Kitner-Triolo
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Elango
authors.initials: E
authors.lastname: Palchamy
authors.affiliation: Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Unit of Clinical and Translational Neuroscience, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA. Electronic address: thambisettym@mail.nih.gov.
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000523:psychology*; D001921:Brain / Q000502:physiology*; D003071:Cognition; D056344:Executive Function; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance; D012306:Risk; D065854:Spatial Navigation; D014796:Visual Perception; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Cognitive performance; Mendelian randomization; Vitamin D