The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients

Objective: The purpose of this study was to examine the relationships between cognitive functioning, whole brain magnetic transfer ratio (MTR) imaging, supratentorial H-1-magnetic resonance spectroscopy imaging ( (HMRSI)-H-1), and conventional T-1 and T-2 imaging in a homogenous sample of SPMS patients. Methods: Nineteen patients underwent a single 90-min imaging session that obtained T-1- and T-2-weighted images and MTR. (HMRSI)-H-1 was obtained on 14 of these patients. Patients underwent a neuropsychological battery, which was used to create an integrated measure of cognitive impairment. Cognitive impairment was the dependent variable in two hierarchical multiple regression analyses in which T-2 lesion load, T-1 lesion load, and MTR or NAA/Cr were entered sequentially. Results: MTR was significantly related to cognitive functioning (DeltaR(2)=0.22, P=0.02) after accounting for T-2 lesion load (DeltaR(2)=0.33, P=0.01) and T-1 lesion load (DeltaR(2)=0.00, P=0.98). NAA/Cr was not significantly related to cognitive functioning. Conclusions: Cognitive dysfunction may act as a clinical marker of normal appearing brain tissue pathology in multiple sclerosis.