Quantitative Susceptibility Mapping of Brain Iron and β-Amyloid in MRI and PET Relating to Cognitive Performance in Cognitively Normal Older Adults
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Lin Chen1, Anja Soldan1, Kenichi Oishi1
1From the F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N Broadway, Room G-25, Baltimore, MD 21205 (L.C., P.C.M.v.Z., X.L.); Department of Radiology and Radiological Sciences (L.C., K.O., A.F., P.C.M.v.Z., X.L.) and Department of Neurology (A.S., M.A.), Johns Hopkins University School of Medicine, Baltimore, Md; and Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, Md (Y.Z.).
Abstract:
Background For individuals with mild cognitive impairment (MCI) or dementia, elevated brain iron together with β-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 β-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 β-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 β-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 β-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, -0.02; 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. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Chiang in this issue.
Insights
Elevated brain iron in cognitively normal older adults is linked to poorer cognitive function, even without high amyloid levels. This suggests iron accumulation is an independent factor impacting cognition in aging brains.
Area of Science:
- Neuroimaging
- Gerontology
- Biochemistry
Background:
- Elevated brain iron and beta-amyloid correlate with cognitive decline in MCI and dementia.
- The impact of brain iron on cognition in cognitively normal older adults requires further investigation.
Purpose of the Study:
- To investigate the effects of cerebral iron and beta-amyloid on cognitive function in cognitively normal older adults using quantitative susceptibility mapping (QSM) MRI and PET.
- To assess the independent and combined effects of brain iron and beta-amyloid on cognitive performance.
Main Methods:
- Secondary analysis of a prospective study involving 150 cognitively normal older adults.
- Quantitative susceptibility mapping (QSM) MRI was used to measure brain iron.
- Positron emission tomography (PET) was used to measure cerebral beta-amyloid in a subset of participants.
- Multiple linear regression and voxel-based analyses examined the relationship between brain iron, beta-amyloid, and cognitive function across 12 brain regions.
Main Results:
- In all participants, higher hippocampal iron content was associated with lower global cognitive scores (p=0.005).
- In the PET subgroup, higher hippocampal iron was linked to poorer episodic memory and visuospatial scores, independent of beta-amyloid levels (p=0.004 and p=0.003, respectively).
- Specific brain regions showed negative correlations between iron, beta-amyloid, and cognitive scores, while beta-amyloid alone did not correlate with global cognition.
Conclusions:
- In cognitively normal older adults, increased cerebral iron load is associated with reduced cognitive performance.
- Brain iron appears to impact cognition independently of beta-amyloid burden in this population.
- QSM MRI and PET imaging provide valuable insights into the role of iron in cognitive aging.
