Abstract
Background Elevated brain iron is a potential marker for neurodegeneration, but its role in predicting onset of mild cognitive impairment (MCI) and prospective cognitive trajectories remains unclear. Purpose To investigate how brain iron and amyloid-β (Aβ) levels, measured using quantitative susceptibility mapping (QSM) MRI and PET, help predict MCI onset and cognitive decline. Materials and Methods In this prospective study conducted between January 2015 and November 2022, cognitively unimpaired older adults underwent baseline QSM MRI. Among the majority with baseline PET data (PET subgroup), cortical Aβ burden was measured. Cox regression and linear mixed-effects models were used to examine associations between baseline tissue susceptibility and time to MCI onset and changes in cognitive scores over time. Results A total of 158 cognitively unimpaired older adults (mean age, 69.5 years ± 8.1 [SD]; 99 women), including 110 individuals (mean age, 68.5 years ± 8.5; 69 women) with data from a PET examination, were evaluated at baseline and followed for up to 7.7 years. Higher baseline susceptibility in the entorhinal cortex and putamen was associated with an increased risk for MCI onset in the overall group and in the PET subgroup (entorhinal cortex, overall group vs PET subgroup: hazard ratio, 2.00 [95% CI: 1.23, 3.23; P = .005] vs 3.59 [95% CI: 1.70, 7.57; P < .001], respectively). In addition, in the PET subgroup, higher baseline susceptibility in the entorhinal cortex (overall, β = -0.020 [standard error of the mean, 0.008; P = .01]; in the entorhinal cortex, β = -0.022 [standard error of the mean, 0.008; P = .008]; and in the putamen, β = -0.018 [standard error of the mean, 0.008; P = .04]) was associated with greater global cognitive decline over time, particularly in the presence of amyloid abnormality. Conclusion Increased tissue magnetic susceptibility in the entorhinal cortex and putamen is a significant predictor of onset of mild cognitive impairment and cognitive decline in cognitively unimpaired older adults, especially those with amyloid neuropathologic abnormalities. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Andreu Arasa in this issue.