Cognitive Impairment and MRI-based Disease Progression in MS PATHS: Variable Susceptibility Across the Lifespan (1334)

Objective: To determine the role of age and education in the association between MRI markers of progression in multiple sclerosis (MS) and cognitive impairment (CI). Background: Brain atrophy (BPF) and T2 lesion volume (T2LV) are known predictors of CI. Using a large heterogeneous real-world sample, we further studied the role of age and education mediating the relationship between BPF, T2LV and CI. Design/Methods: MS PATHS patients who had a standardized MRI within 12 months of their first MS PATHS visit were included. CI was defined as a Processing Speed Test (PST) score ≥ 1 SD worse than predicted from age-, education-, and sex-adjusted normative data. BPF and T2LV were calculated using the MSPie software prototype. Interaction terms in a multivariate model tested whether the association between BPF and T2LV (tertiles) varied across age and education (continuous). Results: 5025 MS patients (age:18–84 years; education:8–20 years; MS duration:0–64 years) were included. The prevalence of CI was 33% in the full sample. CI increased with age, lower educational attainment, lower BPF, and higher T2LV. In the multivariate model, those in the highest BPF tertile had a lower odds of CI across the lifespan [Odds Ratio (OR): 0.25, p Conclusions: With increased age, MS patients may be more susceptible to accumulated tissue damage marked by brain atrophy and T2LV. As MS patients age, CI may be more susceptible to the effects of MRI based markers of disease progression. Preventing brain atrophy and T2 lesions may help to reduce CI in MS. Disclosure: Dr. Charvet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen - reimbursed travel. Dr. Charvet holds stock and/or stock options in Johnson & Johnson. Dr. Charvet has received research support from Biogen. Dr. DeMoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. DeMoor holds stock and/or stock options in Hold stock/stock options in Biogen which sponsored research in which Dr. DeMoor was involved as an investigator. Dr. Fitzgerald has nothing to disclose. Dr. Galioto has nothing to disclose. Dr. Hersh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Novartis, Teva, Genentech, Genzyme, and EMD Serono. Dr. Hersh has received research support from Biogen Idec and PCORI.Dr. Hua has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Novartis, EMD Serono, Genentech, Celgene and TG Therapeutics. Dr. Hyland has received research support from Site PI of studies sponsored by Biogen. Dr. Krupp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Everyday Health, Gerson Lehman, Novartis, RedHill Biopharma, Roche, Shire, and Sanofi-Aventis. Dr. Krupp has received royalty, license fees, or contractual rights payments from Biogen, Reata Pharma, AbbVie Pharmaceuticals, Amicus Therapeutics, SA Inventions, Finkhar Health, Janssen Pharmaceuticals, Eisai, IPSOS, Octapharma, Atara Biotherapeutics, Merck, Research Tech, and ERT Inc. Dr. Krupp has received research support from Biogen and Novartis.Dr. Liao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with employee of Biogen. Dr. Liao holds stock and/or stock options in hold stock/stock options at Biogen which sponsored research in which Dr. Liao was involved as an investigator. Dr. Montalban has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Bayer, Biogen, Celgene. Dr. Montalban has received research support from Received research support through the institution from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceutical. Dr. Mowry has received personal compensation in an editorial capacity for UpToDate. Dr. Mowry has received research support from Biogen, Genzyme, Teva, and Sun Pharma.Dr. Nicholas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting, research, and/or speaking (Biogen, Celgene, EMD Serono, Genentech, MSAA, National MS Society, Novartis, PCORI, and Sanofi).. Dr. Nicholas has received research support from Consulting, research, and/or speaking (Biogen, Celgene, EMD Serono, Genentech, MSAA, National MS Society, Novartis, PCORI, and Sanofi).. Dr. Nos has nothing to disclose. Dr. Rensel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory Board or panel: Serono, Biogen. Consultant: Biogen, Teva, Genzyme and Novartis. Speaker’s Bureau: Novartis, Genzyme, Biogen, Multiple Sclerosis Association of America.. Dr. Rensel has received research support from Grants/Research support: She has received commercial research support from Medimmune, Novartis, Biogen (MS Paths) and Genentech. She has received foundation/society research support from the National Multiple Sclerosis Society. She has received educationa. Dr. Rao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Qr8 Health, Biogen, Sanofi. Dr. Rao has received personal compensation in an editorial capacity for JINS, American Psychologist. Dr. Rao has received royalty, license fees, or contractual rights payments from Cleveland Clinic. Dr. Rao has received research support from Biogen. Dr. Rudick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Rudick holds stock and/or stock options in Holds stock/stock options in Biogen which sponsored research in which Dr. Rudick was involved as an investigator. Dr. Zhovtis Ryerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Zhovtis Ryerson has received personal compensation for serving on speaker bureau for Biogen, Teva, Genentech and advisory board for Biogen and Celgene. Dr. Zhovtis Ryerson has received research support from Biogen. Dr. Tinore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Dr. Tinore has received personal compensation in an editorial capacity for co-editor of Multiple Sclerosis Journal-ETC. Dr. Tinore has received research support from Biogen-Idec, Genzyme, Merck-Serono, Novartis. Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) grant/research support (Biogen, Novartis, Sanofi, and Teva)Dr. Fisher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Fisher holds stock and/or stock options as a full-time employee of and holds stock/stock options in Biogen which sponsored research in which Dr. Fisher was involved as an investigator. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Williams holds stock and/or stock options in Holds stock/stock options in Biogen which sponsored research in which Dr. Williams was involved as an investigator. Dr. Williams holds stock and/or stock options in Holds stock/stock options in Biogen.