Association between metals and metalloids with cognitive status in Mild Cognitive Impairment subjects

Abstract Mild Cognitive Impairment (MCI) is regarded as a transitional state between normal aging and dementia. Several risk factors have been related to MCI and dementia vulnerability. Among these, metals and metalloids have been hypothesized to affect dementia risk. Our objective was to study the associations between metals and metalloids (cadmium, copper, iron, manganese, selenium, zinc) concentrations in serum and cerebrospinal fluid (CSF) with cognitive impairment status of MCI subjects. 144 individuals newly diagnosed with MCI were recruited at Neurology Memory Clinics at Modena and Reggio Emilia Hospitals (Italy) in the period 2019-2022. The concentrations of elements in paired serum/CSF were determined using inductively coupled plasma mass spectrometry. Participants’ global cognitive status was assessed using the Mini-Mental State Examination (MMSE). Muti-adjusted spline regression analyses were performed to assess the relation between the serum/CSF concentrations and MMSE. Median serum and CSF concentrations were generally higher in men than women, except copper in serum and iron in CSF demonstrating higher concentrations in women. A positive linear association emerged between serum iron concentrations and MMSE, while a slight negative one emerged for serum selenium levels. Cadmium in serum was positively associated with MMSE until 0.2 µg/L and then the association became null, while in CSF a U-shaped relation emerged. A U-shaped relation was also observed for serum copper and CSF iron and manganese levels. CSF selenium concentrations were inversely related to MMSE, although above 5 µg/L the curve flattened. Zinc exhibited the same pattern of association in both serum and CSF, i.e., an inverted U-shaped one. These findings suggest that CSF and serum content of the investigated elements may be differently related with global cognitive status in MCI subjects. Higher levels of selenium and zinc, in particular, are associated with lower MMSE score. Key messages • Heavy metals and metalloids display different pattern of association with global cognitive status. • High levels of selenium and zinc are inversely related with global cognitive status in MCI subjects.