Brain iron content in cerebral amyloid angiopathy using quantitative susceptibility mapping

Breni Sharma; Andrew E Beaudin; Emily Cox; Feryal Saad; Krista Nelles; Myrlene Gee; Richard Frayne; David G Gobbi; Richard Camicioli; Eric E Smith; Cheryl R McCreary

doi:10.3389/fnins.2023.1139988

Brain iron content in cerebral amyloid angiopathy using quantitative susceptibility mapping

Front Neurosci. 2023 Apr 17:17:1139988. doi: 10.3389/fnins.2023.1139988. eCollection 2023.

Authors

Breni Sharma^{1

2

3}, Andrew E Beaudin^{1

2

3}, Emily Cox^{1

2

3}, Feryal Saad^{1

2

3

4}, Krista Nelles⁵, Myrlene Gee⁵, Richard Frayne^{1

2

3

4

6

7}, David G Gobbi^{1

2

3

6

7}, Richard Camicioli^{5

8}, Eric E Smith^{1

2

3

4}, Cheryl R McCreary^{1

2

3

4

6}

Affiliations

¹ Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
³ Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
⁴ Seaman Family MR Research Centre, University of Calgary, Calgary, AB, Canada.
⁵ Department of Medicine (Neurology), University of Alberta, Edmonton, AB, Canada.
⁶ Department of Radiology, University of Calgary, Calgary, AB, Canada.
⁷ Calgary Image Processing and Analysis Centre, University of Calgary, Calgary, AB, Canada.
⁸ Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.

Abstract

Introduction: Cerebral amyloid angiopathy (CAA) is a small vessel disease that causes covert and symptomatic brain hemorrhaging. We hypothesized that persons with CAA would have increased brain iron content detectable by quantitative susceptibility mapping (QSM) on magnetic resonance imaging (MRI), and that higher iron content would be associated with worse cognition.

Methods: Participants with CAA (n = 21), mild Alzheimer's disease with dementia (AD-dementia; n = 14), and normal controls (NC; n = 83) underwent 3T MRI. Post-processing QSM techniques were applied to obtain susceptibility values for regions of the frontal and occipital lobe, thalamus, caudate, putamen, pallidum, and hippocampus. Linear regression was used to examine differences between groups, and associations with global cognition, controlling for multiple comparisons using the false discovery rate method.

Results: No differences were found between regions of interest in CAA compared to NC. In AD, the calcarine sulcus had greater iron than NC (β = 0.99 [95% CI: 0.44, 1.53], q < 0.01). However, calcarine sulcus iron content was not associated with global cognition, measured by the Montreal Cognitive Assessment (p > 0.05 for all participants, NC, CAA, and AD).

Discussion: After correcting for multiple comparisons, brain iron content, measured via QSM, was not elevated in CAA compared to NC in this exploratory study.

Keywords: Alzheimer’s disease; cerebral amyloid angiopathy; iron; neuroimaging; quantitative susceptibility mapping.

Grants and funding

This study was supported by the Canadian Consortium on Neurodegeneration in Aging [CCNA; Canadian Institutes of Health Research (CIHR) and partners: CCNA 137794, www.ccna-ccnv.ca], the CIHR (MOP-142175 and FDN-154317), Brain Canada (MIRI2015-3994), Canadian Stroke Network, Heart and Stroke Foundation of Alberta, and the Alzheimer Society of Canada.