Brain iron, cortical atrophy and cognition impairment in cerebral amyloid angiopathy: A quantitative susceptibility mapping study.

BackgroundBrain iron deposition is associated with cognitive impairment in cerebral amyloid angiopathy (CAA) and Alzheimer's disease, but the exact mechanisms remain unclear.ObjectiveTo investigate whether cortical atrophy mediates iron-related cognitive impairment in CAA.MethodsWe prospectively enrolled CAA patients to collect clinical characteristics, conduct global cognitive assessment and magnetic resonance imaging. Iron levels of each brain region were quantified by susceptibility values from quantitative susceptibility mapping. Three-dimensional T1-weighted imaging was collected to calculate cortex volume. For statistical analyses, first, we conducted univariable linear regressions to identify regions with potential associations to cognitive impairment, with p < 0.1 as threshold. Second, we used elastic net analysis to identify regions where iron depositions strongly correlated with cognitive deficits. Finally, we conducted mediation analysis, using these selected regions to test whether iron-related cognitive dysfunction occurs through cortical atrophy.ResultsForty-four patients were included. The median age was 71.5 years old (IQR 62.3, 75.0), and twenty-two were male. Two-thirds of patients presented with mild cognitive impairment or dementia. Elastic net analysis revealed that iron accumulations in the right Rolandic area, left inferior occipital gyrus, left posterior cingulate gyrus and cerebellum were associated with worse cognitive performance. Mediation analysis showed significant total effect of iron in left posterior cingulate gyrus on Mini-Mental State Examination (β = -0.156, p = 0.002), but the average causal mediation effect was insignificant (p = 0.77).ConclusionsWhile regional iron deposition was associated with cognitive impairment in CAA, cortical atrophy did not significantly mediate this relationship in this exploratory study.