Increased iron deposition in putamen and substantia nigra correlates with cognitive function in cerebral small vessel disease: A quantitative susceptibility mapping study

Cerebral small vessel disease (CSVD) is a major contributor to stroke and dementia. Current neuroimaging markers inadequately explain its mechanisms. Sixty-one CSVD patients and 32 age- and sex-matched healthy controls (HC) were retrospectively analyzed. CSVD patients were divided into mild CSVD burden group and severe CSVD burden group according to the total CSVD burden score. The susceptibility values of deep nuclei were obtained based on quantitative susceptibility mapping. The differences in susceptibility values among the three groups were assessed using Kruskal-Wallis H test with Bonferroni correction, and correlations with MoCA-related cognitive scores were evaluated via Spearman’s analysis. CSVD patients exhibited increased susceptibility values in bilateral caudate nucleus, putamen, pallidus, thalamus, substantia nigra (SN), and left red nucleus, and decreased susceptibility values in left amygdala, compared to HC. The susceptibility values in right putamen, left SN pars compacta and bilateral pallidus, SN pars compacta effectively distinguished CSVD patients from HC. Higher iron deposition in putamen and substantia nigra is associated with cognitive impairment. These findings provide evidence that abnormal iron metabolism occurs in multiple deep nuclei, with region-specific accumulation in bilateral putamen and right substantia nigra serving as potential imaging markers of cognitive dysfunction in CSVD.