The MSReactor cognitive screening tests can detect changes in cognitive function in late-onset multiple sclerosis.

Abstract

Introduction: Late-onset MS (LOMS) occurs in up to 12% of people with multiple sclerosis (MS) who are diagnosed at the age of 50 or above. Compared to adult-onset MS (AOMS), there is limited research on cognition in LOMS. At similar disability, LOMS patients have higher impairments in visual learning and working memory compared to AOMS. How these functions change over time in LOMS is an area with a paucity of research. Digital measures to monitor cognitive function may address this gap. This preliminary work compares MSReactor cognitive performance scores between LOMS and AOMS. Objectives/Aims: To detect differences in MSReactor task performance between LOMS and AOMS at baseline and longitudinally. Method(s): The MSReactor platform uses reaction times to broadly screen information processing speed (SRT), attention (CRT) and working memory(OBK) and is currently used in 7 MS centres around Australia. Participants complete clinic-based tests 6-monthly, with the option of additional tests at home. Clinical data was collected via the MSBase registry. Participants with at least one test were selected and divided into those diagnosed at the age of 50 or above (LOMS) or younger (AOMS). Linear regression was used to compare baseline score between LOMS and AOMS, controlling for years of disease duration. Change in reaction time for those with at least three tests was calculated as the difference between the last test performed and baseline test. Additionally, we compared those diagnosed after the age of 60 (Very Late Onset MS (VLOMS)) to those diagnosed under the age of 60. Result(s): From 1376 participants with complete diagnosis data and at least one MSReactor test, 132 were LOMS and 1244 were AOMS. Of these, 19 were defined as VLOMS. Participants with LOMS performed worse than AOMS on all tests at baseline, independent of disease duration (SRT 479 milliseconds (ms) vs 405ms (beta=83.1, p <0.0001); CRT 657ms vs 599ms (beta=69.9, p <0.0001); OBK 1018ms vs 939ms (beta=104, p <0.0001). VLOMS participants performed significantly worse than the remaining cohort at baseline, independent of disease duration (SRT 535ms vs 410ms (beta=136, p <0.0001); CRT 741ms vs 603ms (beta=153.9, p <0.0001); OBK 1087ms vs 945ms (beta=175.2, p <0.01)). In total, 849 participants completed at least 3 MSReactor sessions. In VLOMS (n=15), OBK speed (+114ms; mean follow-up 753 days) slowed over time compared to the remaining cohort (-74ms; mean follow-up 1110 days). In LOMS (n=92), CRT (+10ms; mean follow-up 880 days) slowed compared to the AOMS group (-12ms; mean follow-up 1140 days). Conclusion(s): MSReactor could detect baseline differences in cognitive function between LOMS and AOMS. Longitudinal changes in attention and working memory were detectable in LOMS and VLOMS, compared to a group with an earlier age at diagnosis. Understanding cognitive trajectories in older MS patients is essential to better outcomes and improved trial design. These findings demonstrate the importance of monitoring cognition in these populations. Disclosure of interest: Daniel Merlo reports no disclosures. Chao Zhu reports no disclosures. Melissa Gresle is currently working on observational studies funded by Biogen and Roche. Yi Chao Foong received travel compensation from Biogen. He also receives research funding support from National Health and Medical Research Council, Multiple Sclerosis Research Australia and Australian and New Zealand Association of Neurologists. David Darby is founder & former shareholder of CogState Ltd. He has received honoraria from Biogen, Novartis and Merck. Tomas Kalincik served on scientific advisory boards for the MS International Federation and World Health Organization, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, the steering committee for the Brain Atrophy Initiative by Sanofi Genzyme, and has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck, and research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. Jeannette Lechner-Scott received travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA and Novartis. Michael Barnett served on scientific advisory boards for Biogen, Novartis and Genzyme, and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. Katherine Buzzard has received honoraria for presentations and/or educational support from Biogen, Sanofi Genzyme, Merck, Roche, Alexion and Teva. She serves on medical advisory boards for Merck and Biogen. Bruce Taylor received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen and Novartis, and has served on advisory boards for Biogen, Novartis, Roche and CSL Australia. Nevin John is a PI on commercial MS studies sponsored by Novartis, Roche, Biogen and Sanofi. He has received speaker's honoraria from Merck. He has had conference travel and registration reimbursement from Novartis. Allan Kermode reports no disclosures. Helmut Butzkueven's institution has received compensation for advisory boards or lecture fees from Novartis, Biogen, Merck, UCB Pharma and Roche. His institutions receive research funding from Novartis, Biogen, Merck, Roche, the NHMRC of Australia, The Medical Research Future Fund (Australia), Monash Partners, the Trish MS Foundation, The Pennycook Foundation, and MS Australia. He receives personal compensation as the Managing Director of the MSBase Foundation and from the Oxford Health Policy Forum Brain Health Initiative. Anneke van der Walt served on advisory boards for Novartis, Biogen, Merck and Roche and NervGen. She received unrestricted research grants from Novartis, Biogen, Merck and Roche. She is currently a co-Principal investigator on a co-sponsored observational study with Roche, evaluating a Roche-developed smartphone app, Floodlight-MS. She has received speaker's honoraria and travel support from Novartis, Roche, Biogen and Merck. She serves as the Chief Operating Officer of the MSBase Foundation (not-for-profit). Her primary research support is from the NHMRC of Australia and MS Research Australia.