Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis

Area of Science:

• Neuroimaging
• Neurology
• Biomedical Engineering

Background:

• Deep gray matter iron accumulation is increasingly recognized in multiple sclerosis (MS).
• The cognitive impact of iron accumulation versus atrophy in deep gray matter is not well-understood.
• In vivo MR imaging can measure deep gray matter iron accumulation.

Purpose of the Study:

• To investigate the relationships between cognition and deep gray matter iron in MS.
• To compare the sensitivity of two MR imaging-based iron-susceptibility measures.
• To differentiate the effects of iron accumulation and atrophy on cognition.

Main Methods:

• Forty MS patients and 27 healthy controls underwent 4.7T MR imaging.
• Transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) were used to assess iron.
• Deep gray matter volumes and cognitive function (Brief Repeatable Battery of Neuropsychological Tests) were measured.

Main Results:

• MS patients exhibited reduced memory and processing speed, and smaller deep gray matter volumes compared to controls.
• QSM detected increased iron in the putamen and globus pallidus of MS patients.
• In MS patients, thalamus and putamen volumes correlated with cognitive performance; globus pallidus QSM values remained associated with cognition after controlling for volume.

Conclusions:

• QSM is more sensitive than R2* for detecting deep gray matter iron in MS.
• Both deep gray matter atrophy and iron accumulation negatively impact cognition in MS.
• These effects are separable, indicating distinct pathological contributions to cognitive impairment in MS.