Income, diet, and cognitive function: observational analyses and candidate metabolomic pathways identified by Mendelian randomization - 06/05/26

Doi : 10.1016/j.tjpad.2026.100582 
Xingguang Zhao a, b, 1, Weijian Wu a, 1, Qiaoxuan Zhang c, 1, Mengqian Ouyang d, Haoyu Luo a, Qun Yu a, Yingren Mai a, Zhiyu Cao a, Shaoqing Yang a, Mingsong Xu e, , Jun Liu a, , Wang Liao a,
a Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China 
b School of Public Health, Guangzhou Medical University, Guangzhou, China 
c State Key Laboratory of Dampness Syndrome of Chinese Medicine/Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China 
d Department of Economics, Guangdong Institute of Public Administration, Guangzhou, China 
e The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China 

Corresponding authors at: Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, China. Department of Neurology Institute of Neuroscience Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical University Guangzhou Guangdong 510260 China ⁎⁎ Corresponding author at: The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, China. The Second Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong 510260 China

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Highlights

Multistate Markov models capture bidirectional cognitive transitions over time
Diet mediates socioeconomic disparities in dynamic cognitive trajectories
Cheese and coffee link income to cognition across observational and MR analyses
Gut metabolites connect diet to cognition via amino acid and carnitine pathways
Tryptophan/tyrosine and carnitine/ergothioneine ratios underlie cognitive benefits

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Abstract

Background

Household income has been shown to have impact on cognitive function, with dietary patterns and gut microbiota–related metabolic pathways potentially acting as mediating pathways. Our study integrates observational analyses and Mendelian randomization (MR) to explore these associations.

Methods

The observational analysis included 13,457 participants from the UK Biobank who experienced cognitive transitions. A multistate Markov model was applied to assess the effect of income level on cognitive trajectory, while mediation analysis and quantile regression were performed using baseline data. We applied a two-sample, two-step MR approach utilizing genetic instruments from the IEU Open genome-wide association studies (GWAS) project to determine the causal effects of income on cognition, and further estimate the mediating roles of dietary patterns and 1400 gut metabolites linking income with cognitive performance.

Results

Over a median follow-up of 8.96 years, a total of 14,040 cognitive transitions were recorded (7429 deterioration events and 6801 improvements), with higher income associated with a lower risk of cognitive deterioration. MR analyses confirmed a causal relationship between income and cognitive performance (OR: 2.140, 95% CI: 1.923–2.381; P < 0.001). Notably, cheese and coffee intake demonstrated significant mediation effects in both observational and two-way, two-step MR. The protective effect of cheese appeared to be mediated by gut metabolites, particularly via tryptophan/tyrosine and carnitine/ergothioneine.

Conclusions

Our findings indicate a significant link between income and cognitive performance, cheese and dried fruit may mediate this protective effect through amino acid and carnitine metabolism pathways. Interventions targeting dietary patterns have the potential to prevent cognitive decline attributable to low income.

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Graphical abstract




Image, graphical abstract

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Keywords : Cognitive function, Socioeconomic status, Mendelian randomization, Gut metabolites, Dietary patterns, Dementia


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Vol 13 - N° 7

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