Plasma tryptophan levels are linked to hippocampal integrity and cognitive function in individuals with mild cognitive impairment.

Tryptophan has been shown to improve cognitive functions, but whether these benefits emanate from changes in hippocampal structure or other mechanisms like enhanced serotonin pathways remains unclear. This study aimed to examine the relationship between tryptophan levels and hippocampal volumes in individuals with mild cognitive impairment (MCI) and to determine if changes in hippocampal volume correlate with cognitive function. A total of 499 individuals with MCI were recruited based on ADNI's clinical criteria. Cognitive function was assessed using the ADAS-Cog scale, and hippocampal volumes were measured through MRI using semi-automated Medtronic Surgical Navigation Technologies (SNT). Tryptophan levels in plasma were analyzed using a nuclear magnetic resonance (NMR)-based assay. This study used two models: One unadjusted and another adjusted for covariates such as age, gender, handedness, and ApoE ɛ3 and ɛ4. In both models, higher tryptophan levels were significantly associated with increased bilateral hippocampal volumes, with a stronger effect in the left hippocampus. Furthermore, larger hippocampal volumes were linked to improved cognitive performance. Mediation analysis showed that hippocampal volumes mediated the relationship between plasma tryptophan levels and cognitive function. These findings suggested that elevated plasma tryptophan levels support cognitive health by maintaining hippocampal structural integrity, underscoring its potential role in preserving cognitive function in individuals with MCI.