Pittsburgh compound-B PET and MRI biomarkers of cognition in aging MS patients (P4.347)

Objective: We studied the association of cognitive function with thalamic volume, lobar cortical thickness, cortical [11C] Pittsburgh compound-B (PiB) positron emission tomography (PET) and white matter (WM) PiB binding as a potential myelin marker in an aging MS population. Background: Advanced MRI techniques used in imaging myelin of brain parenchyma are not myelin-specific. In contrast, amyloid tracers such as PiB recently shown to target myelin; PET may be a candidate to image demyelinating diseases. Design/Methods: In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS, with a subset who underwent brain MRI (n=16) and PiB-PET (n=12). One MS patient fulfilled criteria for mild cognitive impairment while another fulfilled criteria for dementia and neither had PiB-PET. Controls from the same cohort were age- and sex-matched (5:1) to MS patients. Quantitative image analyses were performed using automated or semi-automated image processing pipelines. Results: MS patients had lower cognitive z-scores for memory (p=0.03) and language (p=0.02) than controls. MS patients had smaller thalamic volumes (p=0.003), thinner temporal cortices (p=0.001) and thinner frontal cortices (p=0.045) than controls. Thalamic volume loss was associated with decreased attention-executive performance (p=0.02). PiB uptake was reduced in areas of WM hyperintensities compared to normal appearing WM in MS (p=0.0002) and controls (p Conclusions: Thalamic atrophy correlates with lower attention-executive function in late MS and likely reflects WM injury in thalamo-cortical projections. PiB-PET as a potential measure of WM injury, correlates with visuospatial processing and may reflect injury to association area connectivity. Study Supported by: This study was funded by the NIH [R01 AG040042, P50 AG016574, U01 AG006786, C06 RR018898], The Minnesota Partnership for Biotechnology and Medical Genomics, The Elsie and Marvin Dekelboum Family Foundation and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program. Disclosure: Dr. Zeydan has nothing to disclose. Dr. Lowe received personal compensation for activities with Bayer Pharmaceuticals as a consultant. Dr. Przybelski has nothing to disclose. Dr. Schwarz has nothing to disclose. Dr. Tosakulwong has nothing to disclose. Dr. Zuk has nothing to disclose. Dr. Senjem has nothing to disclose. Dr. Gunter has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Mielke has received personal compensation for activities with Lysosomal Therapeutics, Inc. as a consultant. Dr. Mielke has received research support from Biogen. Dr. Benarroch has received personal compensation in an editorial capacity for being a section editor for Neurology. Dr. Rodriguez has received research support from Acorda Therapeutics, Inc. Dr. Machulda has nothing to disclose. Dr. Lesnick has nothing to disclose. Dr. Knopman has received personal compensation for activities with Lundbeck Pharmaceuticals.Dr. Knopman has received research support from Lilly Pharmaceuticals, Biogen and TauRX. Dr. Petersen received personal compensation for activities with Merck, Roche, Genentech, Biogen, and Eli Lilly and Co. Dr. Jack has received personal compensation for activities with Janssen Research & Development, LLC by providing consulting services. Dr. Jack has received research support from the National Institutes of Health (R01-AG011378, RO1-AG041851, RO1-AG037551. Dr. Katarci has received royalty payments from Takeda. Dr. Kantarci has nothing to disclose.