Higher Serum Dopamine Is Associated with Greater Hippocampal Volume and Better Cognitive Function Across the Alzheimer’s Disease Spectrum
Keywords:
Dopamine, Cognitive Function, Alzheimer’s disease, Hippocampus, Brain Volume, Cognitive ImpatientAbstract
Purpose: This study aimed to examine diagnostic-stage differences in serum dopamine, bilateral hippocampal volume, and cognitive performance; tested pooled and diagnosis-specific associations of serum dopamine with hippocampal volume and cognition; evaluated serum dopamine-by-diagnosis interactions; and assessed whether bilateral hippocampal volume statistically mediated the association between serum dopamine and cognitive performance.
Methods and Materials: Baseline ADNI data from 428 participants were analyzed. Associations among serum dopamine, MRI-derived bilateral hippocampal volume, and ADAS-Cog13 performance were examined using adjusted pooled and diagnosis-specific regression models. Mediation analysis tested whether bilateral hippocampal volume mediated the association between serum dopamine and cognitive performance. False discovery rate (FDR) correction was applied.
Findings: Serum dopamine and bilateral hippocampal volume declined across diagnostic stages, whereas cognitive impairment increased. In the pooled cohort, higher serum dopamine was associated with larger bilateral hippocampal volume (standardized β = 0.18, FDR-adjusted q = .002) and better cognitive performance (β = −0.17, q = .006). These associations were strongest in participants with mild cognitive impairment (MCI), in whom higher dopamine was associated with both larger hippocampal volume (β = 0.21, q = .009) and better cognitive performance (β = −0.19, q = .012). Larger bilateral hippocampal volume was independently associated with better cognitive performance (β = −0.35, q < .001). Bilateral hippocampal volume significantly mediated the association between serum dopamine and cognitive performance (indirect effect = −0.063), accounting for 37.1% of the total association.
Conclusion: Higher serum dopamine was associated with greater hippocampal volume and better cognitive performance, partly mediated by hippocampal structural integrity.
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