03c17c4fe44325bd741a4fbc9bf91985 nutrients-17-03483-v2.pdf 53ee500bc3942f39df2fc21f3e8cfb9889fb132f nutrients-17-03483-v2.pdf d614f49d09b0e22a6eb816bdbf7073e3cc8dc567716a6c58dc25377b1c87e8ae nutrients-17-03483-v2.pdf Title: Red Blood Cell Fatty Acid Patterns and Cognitive Functions in Adolescents: A Pooled Analyses with Two Cohort Study Data Sets Subject: Objective: Fatty acids (FAs) play a pivotal role in brain development and cognitive functions during adolescence. We aimed to investigate the association of red blood cell (RBC) FA patterns and several high order neuropsychological functions in adolescents. Methods: The study followed a cross-sectional design. Principal component analysis was applied to 22 FA species previously measured in RBC membranes (exposure variable) to identify FA principal components (PCs) from two cohorts of adolescents in Catalonia, Spain (mean age = 14.53 years). Multiple linear regression was then used to examine associations between PC FAs and cognitive outcomes—working memory, fluid intelligence, and risky decision-making (gain and loss domains). Regression models were adjusted for child sex, age, body mass index, maternal education, and cohort enrollment. Results: Three FA PCs (eigenvalues > 2.0) were retained for the current study: a very-long chain FAs PC, a long-chain omega-6 FA PC and an omega-3 FA PC. The omega-3 FA PC showed a positive association with scores of fluid intelligence (1 = 0.14, CI = 0.05, 0.24, p for trend = 0.003) and risky decision-making (loss domain) (1 = 0.27, CI = 0.03, 0.52, p for trend = 0.030). The very-long chain FAs and long-chain omega-6 FAs patterns showed no significant associations with any cognitive outcome. The PC of omega-3 FA and fluid intelligence associations remained significant after multiple testing corrections. Conclusions: After applying an agnostic approach of multiple FAs in RBC, we found omega-3 FA patterns were positively associated with fluid intelligence among adolescents. Keywords: adolescent health; cognition; fatty acids; principal component analysis Author: Nicolas Ayala-Aldana, Ariadna Pinar-Martí, Marina Ruiz-Rivera, Iolanda Lázaro, Aleix Sala-Vila, Darren R. Healy, Oren Contreras-Rodriguez, Jordi Casanova, Nuria Sola-Valls, Martine Vrijheid and Jordi Julvez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Thu Nov 6 10:17:41 2025 CET ModDate: Thu Nov 6 10:23:35 2025 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 766054 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CRJHCU+PazoMath-Italic Type 1 Builtin yes yes yes 91 0 NFQUXJ+URWPalladioL-Ital Type 1 Custom yes yes yes 92 0 DYURDS+URWPalladioL-Bold Type 1 Custom yes yes yes 93 0 NWMVUP+URWPalladioL-Roma Type 1 Custom yes yes yes 94 0 QNALHW+VnURWPalladioL Type 1 Custom yes yes yes 95 0 XCNMIU+CMSY10 Type 1 Builtin yes yes yes 141 0 ORYLMY+EURM10 Type 1 Builtin yes yes yes 142 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 220 0 KOHOHA+PalatinoLinotype TrueType WinAnsi yes yes no 215 0 IUOUHH+PazoMath-BoldItalic Type 1 Builtin yes yes yes 244 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-11-26 03:10:20 CET RepresentationInformation: nutrients-17-03483-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-11-25 15:51:33 CET Size: 766054 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 417 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Material and Methods Children: Item: Title: Study Design and Participants Item: Title: Fatty Acid Determination Item: Title: Primary Outcomes Item: Title: Reduction in Dimensionality of Fatty Acids: Principal Component Analysis Item: Title: Statistical Analysis Item: Title: Results Item: Title: Discussion Item: Title: Conclusions Item: Title: References Info: Title: Red Blood Cell Fatty Acid Patterns and Cognitive Functions in Adolescents: A Pooled Analyses with Two Cohort Study Data Sets Author: Nicolas Ayala-Aldana, Ariadna Pinar-Martí, Marina Ruiz-Rivera, Iolanda Lázaro, Aleix Sala-Vila, Darren R. Healy, Oren Contreras-Rodriguez, Jordi Casanova, Nuria Sola-Valls, Martine Vrijheid and Jordi Julvez Subject: Objective: Fatty acids (FAs) play a pivotal role in brain development and cognitive functions during adolescence. We aimed to investigate the association of red blood cell (RBC) FA patterns and several high order neuropsychological functions in adolescents. Methods: The study followed a cross-sectional design. Principal component analysis was applied to 22 FA species previously measured in RBC membranes (exposure variable) to identify FA principal components (PCs) from two cohorts of adolescents in Catalonia, Spain (mean age = 14.53 years). Multiple linear regression was then used to examine associations between PC FAs and cognitive outcomes—working memory, fluid intelligence, and risky decision-making (gain and loss domains). Regression models were adjusted for child sex, age, body mass index, maternal education, and cohort enrollment. Results: Three FA PCs (eigenvalues > 2.0) were retained for the current study: a very-long chain FAs PC, a long-chain omega-6 FA PC and an omega-3 FA PC. The omega-3 FA PC showed a positive association with scores of fluid intelligence (1 = 0.14, CI = 0.05, 0.24, p for trend = 0.003) and risky decision-making (loss domain) (1 = 0.27, CI = 0.03, 0.52, p for trend = 0.030). The very-long chain FAs and long-chain omega-6 FAs patterns showed no significant associations with any cognitive outcome. The PC of omega-3 FA and fluid intelligence associations remained significant after multiple testing corrections. Conclusions: After applying an agnostic approach of multiple FAs in RBC, we found omega-3 FA patterns were positively associated with fluid intelligence among adolescents. 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