Quantitative Susceptibility Mapping of Brain Iron and β-Amyloid in MRI and PET Relating to Cognitive Performance in Cognitively Normal Older Adults

Background: For individuals with mild cognitive impairment (MCI) or dementia, elevated brain iron together with b-amyloid is associated with lower cognitive functioning. But this needs further investigation among cognitively normal older adults. Purpose: To investigate via quantitative susceptibility mapping (QSM) in MRI and PET how cerebral iron together with b-amyloid affects cognition among cognitively normal older adults. Materials and Methods: In this secondary analysis of a prospective study, cognitively normal older adults underwent QSM MRI to measure brain iron. A majority underwent PET to measure cerebral b-amyloid within 30 days of MRI. Multiple linear regression analyses were performed for 12 cortical and subcortical gray matter regions to assess the effect of brain iron on cognitive functions. Voxel-based analyses investigated the associations between tissue iron and b-amyloid load and their relationship to cognitive performance. Results: Evaluated were 150 cognitively normal older adults (mean age, 69 years ± 8 [standard deviation]; 93 women). Of 150, 97 underwent PET; 22 of the 97 (mean age, 71 years ± 6; 13 women) were positive for β-amyloid. In all participants, brain iron content in the hippocampus negatively correlated with global cognitive composite score (standardized β = -0.24; 95% CI: -0.40, -0.07; P = .005). In the PET subgroup, brain iron in the hippocampus negatively correlated with episodic memory (β = -0.24; 95% CI: -0.40, -0.08; P = .004) and visuospatial score (β = -0.34; 95% CI: -0.56, -0.12; P = .003) independent of β-amyloid burden. Both negative and positive correlations between brain iron and b-amyloid were observed in the PET subgroup, revealing clusters where brain iron content negatively correlated with β-amyloid and global cognitive scores (eg, in the frontal cortex: β = -0.13; 95% CI: -0.23, 20.02; P = .02). No clusters showed associations between β-amyloid and global cognition. Conclusion: Among cognitively normal older adults, quantitative susceptibility mapping in MRI and PET indicated that elevated cerebral iron load was related to lower cognitive performance independent of β-amyloid.