Associations between cognitive reserve, iron deposition in the basal ganglia, and cognitive function in mild cognitive impairment

Objective This research aims to investigate the putative mechanisms underlying the association between iron deposition and cognition in mild cognitive impairment (MCI). It also seeks to analyze whether the relationship between cognitive reserve (CR) and cognition may be mediated by iron deposition. Methods In total, 109 individuals with MCI and 90 healthy controls (HCs) were enrolled to evaluate iron deposition in the basal ganglia using quantitative susceptibility mapping (QSM). The Cognitive Reserve Index questionnaire (CRIq) was used to evaluate the comprehensive CR of participants in both groups. QSM values in the basal ganglia were compared between the two groups, and Spearman correlation analyses were performed to examine the associations between CR, QSM values, and cognition. Mediation analyses using a bootstrapping approach were conducted to investigate the correlations between CR, QSM values, and cognition. Results The MCI group exhibited significantly higher QSM values in the bilateral putamen (PU), substantia nigra (SN), red nucleus (RN), and right caudate nucleus (CA) compared to HCs. After adjusting for age and sex, QSM values in the left RN were negatively correlated with Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Auditory Verbal Learning Test (AVLT) long-delay recall, and AVLT recognition scores. In contrast, QSM values in the bilateral RN and left SN were negatively correlated with Clock Drawing Test (CDT) scores in the MCI group. CRIq scores were significantly negatively correlated with QSM values in the bilateral RN and right SN. Meanwhile, QSM values in the bilateral RN partially mediated the association between the CRIq scores and cognition in the MCI group. Conclusion Individuals with MCI who have different CR levels exhibited differences in iron deposition in the basal ganglia. Comprehensive CR may delay the decline of cognitive function by regulating iron deposition in the bilateral RN during the MCI stage.