Association between serum tricosanoic acid and cognitive function in older adults: findings from the NHANES and GEO databases

Introduction: With global aging, dementia prevalence rises. While long-chain saturated fatty acids show anti-cognitive decline potential, serum tricosanoic acid (C23:0)'s role in brain regions and cognition remains unclear.

Methods: To confirm the association between C23:0 and cognition in the population, we analyzed gene expression data from the Alzheimer's disease (AD) brain gene chip data set (GSE118553) available in the Gene Expression Omnibus (GEO) database. Additionally, we examined data from 1,127 adults aged 60 years and older who participated in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. To explore potential metabolic pathways and mechanisms linking C23:0 to cognitive aging, the computational platform METAFlux was employed.

Results: Differential gene expression analysis identified 335 downregulated and 477 upregulated genes in AD frontal cortex. Metabolite analysis showed 20 upregulated and 37 downregulated nutrients (including C23:0) in AD vs. controls. Population-level analysis (NHANES, n = 1,127) confirmed higher serum C23:0 associated with better cognitive function.

Discussion: This study provides strong evidence for frontal cortex-specific reduced C23:0 in AD and highlights its potential as a serum cognitive marker.

Alzheimer’s disease (AD); GEO; NHANES; older adults; tricosanoic acid.