Cerebral quantitative susceptibility mapping predicts amyloid-β-related cognitive decline

The large variance in cognitive deterioration in subjects who test positive for amyloid-beta by positron emission tomography indicates that convergent pathologies, such as iron accumulation, might combine with amyloid-beta to accelerate Alzheimer's disease progression. Here, we applied quantitative susceptibility mapping, a relatively new magnetic resonance imaging method sensitive to tissue iron, to assess the relationship between iron, amyloid-beta load, and cognitive decline in 117 subjects who underwent baseline magnetic resonance imaging and amyloid-beta positron emission tomography from the Australian Imaging, Biomarkers and Lifestyle study (AIBL). Cognitive function data were collected every 18 months for up to 6 years from 100 volunteers who were either cognitively normal (n = 64) or diagnosed with mild cognitive impairment (n = 17) or Alzheimer's disease (n = 19). Among participants with amyloid pathology (n = 45), higher hippocampal quantitative susceptibility mapping levels predicted accelerated deterioration in composite cognition tests for episodic memory [beta(standard error) = -0.169 (0.034), P = 9.2 x 10(-7)], executive function [b(standard error) = -0.139 (0.048), P = 0.004), and attention [beta(standard error) = -0.074 (0.029), P = 0.012]. Deteriorating performance in a composite of language tests was predicted by higher quantitative susceptibility mapping levels in temporal lobe [b(standard error) = -0.104 (0.05), P = 0.036] and frontal lobe [beta(standard error) = -0.154 (0.055), P = 0.006]. These findings indicate that brain iron might combine with amyloid-beta to accelerate clinical progression and that quantitative susceptibility mapping could be used in combination with amyloid-beta positron emission tomography to stratify individuals at risk of decline.