Contributions
Abstract: EP1770
Type: ePoster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: Total lesion volume is commonly evaluated in multiple sclerosis (MS) as an indicator of overall disease pathology. However, lesion volume often correlates poorly with cognitive outcomes. Newer techniques allow for the assessment of a global outcome measure which accounts for the number of actual region-to-region connections impaired by individual lesions (based on their location). This measure can be derived from typical clinical MRI and may be better associated with cognitive decline than total lesion volume.
Objective: To determine whether whole brain tract disruption caused by lesions is a better predictor of cognitive decline than total lesion volume in MS.
Methods: The Network Modification tool was used to quantify tract disruption between gray matter structures caused by white matter lesions in 120 subjects with MS. Linear regressions were used to model cognitive decline with either total lesion volume or whole brain tract disruption, controlling for age and gender. Cognitive decline was assessed via consensus cognitive tests of processing speed, visual memory, verbal memory, and attention (as measured by Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised total learned, California Verbal Learning Test total learned, and Paced Auditory Serial Addition Test).
Results: For prediction of processing speed, adjusted R2 was 0.222 for the total lesion volume model and 0.263 for the whole brain tract disruption model - an 18% relative increase in explanatory power
(4% absolute increase). Similar increases in adjusted R2 were observed in models predicting visual memory (0.120 vs. 0.143), verbal memory (0.147 vs. 0.154), and attention (0.075 vs. 0.083).
Conclusions: Although still describing a minority of the variance in cognitive decline, a single measure of global tract disruption is more strongly related to a variety of cognitive deficits in MS than total lesion volume.
Disclosure:
Tom Fuchs, Sanjeevani Choudhery, Keith Carolus, Niels P. Bergsland, Deepa Ramasamy, and Dejan Jakimovki have nothing to disclose.
Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono,Genzyme, Sanofi, Novartis, Acorda.
R Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Claret-Medical, Celgene for speaking and consultant fees. He received financial support for research activities from Claret Medical, Genzyme-Sanofi, QuintilesIMS Health, Intekrin-Coherus, Novartis and Intekrin-Coherus.
Ralph Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.
Abstract: EP1770
Type: ePoster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: Total lesion volume is commonly evaluated in multiple sclerosis (MS) as an indicator of overall disease pathology. However, lesion volume often correlates poorly with cognitive outcomes. Newer techniques allow for the assessment of a global outcome measure which accounts for the number of actual region-to-region connections impaired by individual lesions (based on their location). This measure can be derived from typical clinical MRI and may be better associated with cognitive decline than total lesion volume.
Objective: To determine whether whole brain tract disruption caused by lesions is a better predictor of cognitive decline than total lesion volume in MS.
Methods: The Network Modification tool was used to quantify tract disruption between gray matter structures caused by white matter lesions in 120 subjects with MS. Linear regressions were used to model cognitive decline with either total lesion volume or whole brain tract disruption, controlling for age and gender. Cognitive decline was assessed via consensus cognitive tests of processing speed, visual memory, verbal memory, and attention (as measured by Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised total learned, California Verbal Learning Test total learned, and Paced Auditory Serial Addition Test).
Results: For prediction of processing speed, adjusted R2 was 0.222 for the total lesion volume model and 0.263 for the whole brain tract disruption model - an 18% relative increase in explanatory power
(4% absolute increase). Similar increases in adjusted R2 were observed in models predicting visual memory (0.120 vs. 0.143), verbal memory (0.147 vs. 0.154), and attention (0.075 vs. 0.083).
Conclusions: Although still describing a minority of the variance in cognitive decline, a single measure of global tract disruption is more strongly related to a variety of cognitive deficits in MS than total lesion volume.
Disclosure:
Tom Fuchs, Sanjeevani Choudhery, Keith Carolus, Niels P. Bergsland, Deepa Ramasamy, and Dejan Jakimovki have nothing to disclose.
Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono,Genzyme, Sanofi, Novartis, Acorda.
R Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Claret-Medical, Celgene for speaking and consultant fees. He received financial support for research activities from Claret Medical, Genzyme-Sanofi, QuintilesIMS Health, Intekrin-Coherus, Novartis and Intekrin-Coherus.
Ralph Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.