A Metallomic Approach to Assess the Associations between Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: A Cross-sectional and Longitudinal Study

Abstract

BACKGROUND Alzheimer’s disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis. The present study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. METHODS All participants (controls, aMCI, and AD) underwent baseline cognitive tests, which included the Mini-Mental State Examination (MMSE) and plasma biomarker examinations. We conducted a trend analysis for the cognitive tests and plasma trace elements and examined the correlations between the latter and annual MMSE changes during follow-up. RESULTS An increase in the disease severity was linked to lowered boron (B), bismuth (Bi), thorium (Th), and uranium (U) plasma concentrations (adjusted P < 0.05). “B”, mercury (Hg) and “Th” levels could detect different cognitive stages. “B” displayed high area under the receiver operating characteristic curves (AUCs) for aMCI and AD versus controls (97.6%, cut-off value: ≤73.1 ug/l and 100%, cut-off value: ≤47.1 ug/l, respectively). “Hg” displayed the highest AUC result to differentiate AD from aMCI (79.9%, cut-off value: ≤1.02 ug/l). Higher baseline levels of calcium (r = 0.50, p = 0.026) were associated with less annual cognitive decline. While higher baseline levels of “B” (r=-0.70, p = 0.001), zirconium (r=-0.58, p = 0.007), “Th” (r=-0.52, p = 0.020) were associated with rapid annual cognitive decline in the aMCI group, those of manganese (r=-0.91, p = 0.035) were associated with rapid annual cognitive decline in the AD group. CONCLUSION Plasma metal level biomarkers can be used as an in vivo tool to study and identify patients with aMCI and AD.