Metabolites and Cognitive Decline in a Puerto Rican Cohort

Issue title: Omics Approaches in Alzheimer’s Disease Research

Guest editors: Sudeshna Das

Article type: Research Article

Authors: Gordon, Scott^a | Lee, Jong Soo^{b; c} | Scott, Tammy M.^d | Bhupathiraju, Shilpa^{e; f} | Ordovas, Jose^g | Kelly, Rachel S.^f | Tucker, Katherine L.^{c; h} | Palacios, Natalia^{c; e; i; j; *}

Affiliations: [a] Department of Computer Science, University of Massachusetts Lowell, Lowell, MA, USA | [b] Department of Mathematical Sciences, University of Massachusetts Lowell, Lowell, MA, USA | [c] Center for Population Health, University of Massachusetts Lowell, Lowell, MA, USA | [d] Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA | [e] Department of Nutrition, Harvard School of Public Health, Boston, MA, USA | [f] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA | [g] Jean Mayer USDA Human Research Center on Aging, Tufts University, Boston, MA, USA | [h] Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, USA | [i] Department of Public Health, University of Massachusetts Lowell, Lowell, MA, USA | [j] Geriatric Research Education Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA

Correspondence: [*] Correspondence to: Natalia Palacios, PhD, Department of Public Health, University of Massachusetts Lowell, 61 Wilder Street, Suite 540-K, Lowell, MA 01854, USA. Tel.: +1 978 934 5373; E-mail: [email protected].

Abstract: Background:Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer’s disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans. Objective:This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population. Methods:We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory. Results:We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory. Conclusions:The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline.

Keywords: Alzheimer’s disease, cognitive decline, Latinos, metabolomics, Puerto rican

DOI: 10.3233/JAD-230053

Journal: Journal of Alzheimer's Disease, vol. 99, no. s2, pp. S345-S353, 2024