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

Scott Ayton, Amir Fazlollahi, Pierrick Bourgeat, Parnesh Raniga, Amanda Ng, Yen Ying Lim, Ibrahima Diouf, Shawna Farquharson, Jurgen Fripp, David Ames, James Doecke, Patricia Desmond, Roger Ordidge, Colin L. Masters, Christopher C. Rowe, Paul Maruff, Victor L. Villemagne, Olivier Salvado, Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group, Ashley I. Bush

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The large variance in cognitive deterioration in subjects who test positive for amyloid-β by positron emission tomography indicates that convergent pathologies, such as iron accumulation, might combine with amyloid-β 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-β load, and cognitive decline in 117 subjects who underwent baseline magnetic resonance imaging and amyloid-β 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 [β(standard error) = -0.169 (0.034), P = 9.2 × 10 -7 ], executive function [β(standard error) = -0.139 (0.048), P = 0.004), and attention [β(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 [β(standard error) = -0.104 (0.05), P = 0.036] and frontal lobe [β(standard error) = -0.154 (0.055), P = 0.006]. These findings indicate that brain iron might combine with amyloid-β to accelerate clinical progression and that quantitative susceptibility mapping could be used in combination with amyloid-β positron emission tomography to stratify individuals at risk of decline.

Original languageEnglish
Pages (from-to)2112-2119
Number of pages8
Issue number8
Publication statusPublished - Aug 2017
Externally publishedYes


  • Alzheimer's
  • cognitive decline
  • iron
  • MRI
  • Quantitative Susceptibility Mapping

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