Abstract
Background
Alzheimer's disease (AD) is characterized by decreased cerebral blood flow (CBF) and abnormal iron deposition, whereas their relationship remains unclear.
Objective
To investigate the spatial pattern of CBF-iron deposition coupling across the AD spectrum and its associations with cognition, plasma biomarkers, and inflammation.
Methods
34 AD dementia, 86 mild cognitive impairment (MCI), and 26 cognitively normal (CN) were enrolled. Voxel-wise CBF-susceptibility coupling was calculated using three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping (QSM). Whole-brain region-based analyses of CBF, QSM, and CBF-susceptibility coupling were subsequently performed. Correlation and mediation analyses were conducted to evaluate the relationships of CBF-susceptibility coupling with plasma biomarkers, inflammatory factors, and cognitive function.
Results
CBF was significantly reduced in the AD dementia group and MCI group. No significant group differences were observed in QSM susceptibility. The AD dementia group showed significantly lower CBF-susceptibility coupling in multiple brain regions than CN and MCI groups, which was positively correlated with Mini-Mental State Examination (MMSE), Animal Fluency Test scores, and the plasma amyloid-β 42/40 (Aβ42/Aβ40) ratio. In the MCI group, coupling values were negatively correlated with IL-2 levels. CBF-susceptibility coupling in the bilateral supplementary motor areas of AD patients partially mediated the association between Aβ42/Aβ40 ratio and MMSE.
Conclusions
CBF-susceptibility coupling is significantly decreased in AD dementia and appears more sensitive than single-modality measures, and is associated with cognitive decline, amyloid pathology, and inflammation. These findings suggest that disrupted CBF-iron metabolism coupling may be a pathogenic mechanism underlying cognitive impairment in AD, possibly driven by early neuroinflammation.
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