Abstract Details

Title Concordance Between Structural and Functional Connectivity Reflects Available Cognitive Reserve in Multiple Sclerosis During Cognitive Rehabilitation

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-025

Objective

Determine whether preserved functional connectivity, a potential proxy for cognitive reserve, moderates the relationship between white matter (WM) tract disruption and individual responsiveness to restorative cognitive rehabilitation in patients with multiple sclerosis (MS).

Background

Preservation of normal functional connectivity has been shown to mitigate the association between focal WM tract disruption and cognition in people with MS and relates to traditional proxies for cognitive reserve. This discrepancy between structural disconnection and functional connectivity may be an MRI marker for cognitive reserve, and therefore may help explain differences in individual responses to restorative cognitive rehabilitation.

Design/Methods

51 people with MS (35 relapsing-remitting, 16 progressive) were recruited for a 12-week restorative cognitive rehabilitation program. Each participant underwent neuropsychological evaluation pre- and post-rehabilitation. Conventional measures of neuropathology were obtained: gray matter volume (GMV) and T2-lesion volume (T2LV). Additionally, white matter tract disruption was measured between pairs of GM regions. In a sub-group for which resting-state fMRI was also available (n=25) pairwise deviation in functional connectivity was measured relative to age- and sex-matched healthy controls (N=29).

Results Overall, subjects exhibited a statistically significant increase in cognitive processing speed following rehabilitation (t=3.91, p<0.001). After accounting for age, sex, GMV, disease duration, and T2LV, prediction of treatment efficacy was improved in a model also including WM tract disruption in a localized network of four region-pairs centered on the precuneus in the left hemisphere (ΔR²=0.144, p=0.024). This effect of local tract disruption on treatment efficacy was moderated by mean deviation in functional connectivity of region-pairs included in the network (standardized-β=-0.716, p=0.040).

Conclusions Preservation of normal functional connectivity buffers against the negative impact of increased tract disruption on cognitive rehabilitation efficacy in MS. This effect functions similarly to cognitive reserve and may help explain why some individuals retain their capacity to improve cognition, despite accumulation of neuropathology.

Authors/Disclosures
Tom Fuchs (Buffalo Neuroimaging Analysis Center) PRESENTER	Mr. Fuchs has nothing to disclose.
	No disclosure on file
Ralph H. Benedict, PhD (University At Buffalo)	Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic Therapeutics. Dr. Benedict has received intellectual property interests from a discovery or technology relating to health care.
Alexander Bartnik	No disclosure on file
	No disclosure on file
Leigh E. Charvet, PhD (NYU Langone)	Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Healthcare. Dr. Charvet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for YBrain. Dr. Charvet has stock in Johnson&Johnson.
Michael Shaw	Mr. Shaw has nothing to disclose.
	No disclosure on file
	No disclosure on file
Faizan Yasin (WVU Neurology)	No disclosure on file
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center)	Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.

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