Seyed-Parsa Hojjat1,2, Charles Grady Cantrell3, Timothy J Carroll4,3,5, Rita Vitorino5, Anthony Feinstein6,7, Lying Zhang5, Sean P Symons5,7, Sarah A Morrow8, Liesly Lee9,7, Paul O'Connor5,7, Richard I Aviv5,7. 1. Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada Parsa.Hojjat@sunnybrook.ca. 2. University of Toronto, Toronto, ON, Canada Parsa.Hojjat@sunnybrook.ca. 3. Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA. 4. Department of Radiology, Northwestern University, Chicago, IL, USA. 5. Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. 6. Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. 7. University of Toronto, Toronto, ON, Canada. 8. Department of Clinical Neurological Sciences, Western University, London, ON, Canada. 9. Department of Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Abstract
BACKGROUND: Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. METHODS: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. RESULTS: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). CONCLUSION: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.
BACKGROUND:Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. METHODS: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. RESULTS: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). CONCLUSION: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.
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