Associations between metabolic syndrome and regional brain iron depositions and cognitive function in middle-aged and older adults: A two multinational cohort study.

INTRODUCTION: The alterations of regional brain iron in patients with metabolic syndrome (Mets) and its relationship with cognitive function remain unclear. METHODS: These analyses utilized data from two prospective cohorts, from the UK Biobank (UKB) (21,346 participants) and from Jinan, China (224 participants). We capitalized brain iron in the striatum and thalamus of UKB. Then voxel-based analysis of quantitative susceptibility mapping (QSM) was used to detect regional susceptibility value alteration in our cohort and their relationship with cognitive function was assessed using linear regression. RESULTS: Mets patients exhibited iron deposition in the striatum and thalamus, which was mainly associated with hyperglycemia and elevated triglycerides among the risk factors in UKB. Mets patients exhibited iron deposition in the right caudate nucleus, which was associated with cognitive decline in the Jinan cohort. DISCUSSION: Regional brain iron deposition might serve as a neuroimaging biomarker of Mets severity and a potential mechanism for cognitive decline. HIGHLIGHTS: Iron deposition in deep gray matter nuclei was found in patients with metabolic syndrome (Mets) in both UK Biobank (UKB) and Jinan cohort. Iron deposition in the deep gray matter nuclei of Mets in UKB was mainly related to hyperglycemia and elevated triglycerides among metabolic risk factors. The UKB longitudinal study found that the susceptibility values of the caudate nucleus and putamen of Mets patients increased significantly with age compared to healthy controls. Patients with Mets exhibited poorer cognitive function, which was closely associated with iron deposition in the right caudate nucleus in the Jinan cohort. The association between iron deposition and cognition was more concentrated in the elderly, smokers and drinkers, and those with low years of education.