Early extra-motor brain iron accumulation is linked to cognitive deficits in sporadic early-stage amyotrophic lateral sclerosis patients

Motivation: Understanding iron metabolism abnormalities in early-stage ALS is essential for revealing the disease's multisystemic effects and link to cognitive deficits. Goal(s): This study aims to identify brain iron accumulation patterns through quantitative susceptibility mapping (QSM) and assess their connection to cognitive impairments in newly diagnosed sporadic ALS patients. Approach: We performed voxel-based whole-brain QSM analysis in 53 early-stage ALS patients and 50 healthy controls, correlating iron deposition patterns with clinical assessments and cognitive scores. Results: Significant iron accumulation in motor and extra-motor regions of ALS patients correlates with cognitive deficits, highlighting QSM's potential for early neuroanatomical detection in ALS. Impact: This study identifies widespread brain iron accumulation as a hallmark of early-stage ALS, linked to cognitive decline. Findings highlight QSM's potential as an early diagnostic tool and suggest iron metabolism as a promising therapeutic target.