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Background and Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods., Methods: We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods., Results: A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse., Discussion: Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family., Classification of Evidence: This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies.

Background: Observational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials., Objective: To describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age., Methods: MS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18., Results: Eighty-seven patients initiating fingolimod and 52 initiating ocrelizumab met the inclusion criteria. Before starting fingolimod, mean annualized relapse rate was 0.43 (95 % CI: 0.29 - 0.65) and 78 % developed new T2 lesions while during treatment it was 0.12 (95 % CI: 0.08 - 1.9) and 47 % developed new T2 lesions. In the ocrelizumab group, the mean annualized relapse rate prior to initiation of treatment was 0.64 (95 % CI: 0.38-1.09) and a total of 83 % of patients developed new T2 lesions while during treatment it was 0.09 (95 % CI: 0.04-0.21) and none developed new T2 lesions., Conclusion: This study highlights the importance of evaluating current treatment methods and provides insights about the agents in the ongoing phase III trial comparing fingolimod and ocrelizumab., Competing Interests: Declaration of competing interest ZN, TC, MW, AV, TL, NSH, TCH, MR, JT, TSCH, SM, MR, AA had no disclosures. MG has received research funding from Roche and Pfizer. LB received funding from NIH, Harvard Medical School Shore grant, ROHHAD Fight, Inc. She received honoraria from Novartis. She participated in clinical trials with Biogen, Alexion and Genentech/Roche. She is a consultant to the national Vaccine Injury Compensation Program and Massachusetts Department of Public Health. L Krupp has received advisory board/consulting fees, travel and meal allowances, and/or research funding from Sanofi-Aventis, Biogen, Novartis, Eisai, Roche, Gerson Lehrman, Janssen, Cambridge Medical Technologies and Medergy Marketing over the last three years. She is also a non-compensated consultant and/or advisory board member with Novartis and Celgene. Dr. Krupp receives royalties for use of the Fatigue Severity Scale by various biopharmaceutical entities. J Rose has current research funding from NMSS, Biogen, VA, and NIH. S Guye, C Liu and C Manlius are employee of F. Hoffmann-la Roche Ltd. E Waubant has participated in multicenter clinical trials funded by Genentech, Alexion and Biogen. She has current support from the NIH, NMSS, PCORI, CMSC, Department of Defense and Race to Erase MS. This study was Sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Network funding provided by National MS Society (SI-1808–32,326)., (Copyright © 2024. Published by Elsevier B.V.)

Introduction/aims: Data regarding weight, height/length, and growth status of patients with spinal muscular atrophy (SMA) who have received only supportive care are limited. This cross-sectional study describes these measurements in patients with Type 1 and Types 2/3 SMA and compares them with reference values from typically developing children., Methods: Retrospective baseline data from three sites in the Pediatric Neuromuscular Clinical Research Network (Boston, New York, Philadelphia) were used. Descriptive statistics for weight, height/length, body mass index-for-age, as well as weight-for-length and absolute and relative deviations from reference values (ie, 50th percentile from World Health Organization/Centers for Disease Control growth charts) were calculated. Furthermore, growth status was reported., Results: A total of 91 genetically confirmed patients with SMA receiving optimal supportive care and without any disease-modifying treatment were stratified into Types 1 (n = 28) and 2/3 SMA (n = 63). Patients with Type 1 SMA weighed significantly less (median = -7.5%) compared with reference values and patients with Types 2/3 SMA were significantly shorter (mean = -3.0%) compared with reference values. The median weight was considerably below the 50th percentile in both groups of patients, even if they received a high standard of care and proactive feeding support., Discussion: More research is needed to understand which factors influence growth longitudinally, and how to accurately capture growth in patients with SMA. Further research should investigate the best time to provide feeding support to avoid underweight, especially in patients with Type 1, and how to avoid the risk of overfeeding, especially in patients with Types 2/3 SMA., (© 2022 F. Hoffmann-La Roche Ltd. Muscle & Nerve published by Wiley Periodicals LLC.)

Objectives: An engaged lifestyle has been linked to measures of functional ability in everyday life. However, the underlying mechanism of this link is still understudied. We propose working memory as a potential mediator of this relation., Methods: Modeling data of 158 older adults with a latent-variables approach, we examined whether working memory mediated the relation between an engaged lifestyle, that is, intellectual, social, and physical activities, and functional ability, that is, self-reported everyday failures and test-based everyday performance., Results: Working memory was found to fully mediate the relation between gaming activities and test-based everyday performance. Furthermore, we found a negative association between sports activities and self-reported everyday failures not mediated through working memory, indicating that individuals who reported high levels of sports activities reported fewer everyday cognitive failures. All other lifestyle activities were, however, neither directly nor indirectly associated with functional ability., Discussion: Working memory is one pathway by which gaming activities are related to test-based measures of functional ability in everyday life. Given the overlapping cognitive demands of working memory, gaming activities, and the test-based measure of functional ability, the findings suggest that while an engaged lifestyle can benefit functional ability, those benefits may be limited to highly similar domains., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In the context of the fourth revolution in healthcare technologies, leveraging monitoring and personalization across different domains becomes a key factor for providing useful services to maintain and promote well-being. This is even more crucial for older people, with aging being a complex multi-dimensional and multi-factorial process which can lead to frailty. The NESTORE project was recently funded by the EU Commission with the aim of supporting healthy older people to sustain their well-being and capacity to live independently. It is based on a multi-dimensional model of the healthy aging process that covers physical activity, nutrition, cognition, and social activity. NESTORE is based on the paradigm of the human-in-the-loop cyber-physical system that, exploiting the availability of Internet of Things technologies combined with analytics in the cloud, provides a virtual coaching system to support healthy aging. This work describes the design of the NESTORE methodology and its IoT architecture. We first model the end-user under several domains, then we present the NESTORE system that, analyzing relevant key-markers, provides coaching activities and personalized feedback to the user. Finally, we describe the validation strategy to assess the effectiveness of NESTORE as a coaching platform for healthy aging., (Copyright © 2020 Palumbo, Crivello, Furfari, Girolami, Mastropietro, Manferdelli, Röcke, Guye, Salvá Casanovas, Caon, Carrino, Abou Khaled, Mugellini, Denna, Mauri, Ward, Subías-Beltrán, Orte, Candea, Candea and Rizzo.)

Little is still known about the neuroanatomical substrates related to changes in specific cognitive abilities in the course of healthy aging, and the existing evidence is predominantly based on cross-sectional studies. However, to understand the intricate dynamics between developmental changes in brain structure and changes in cognitive ability, longitudinal studies are needed. In the present article, we review the current longitudinal evidence on correlated changes between magnetic resonance imaging-derived measures of brain structure (e.g. gray matter/white matter volume, cortical thickness), and laboratory-based measures of fluid cognitive ability (e.g. intelligence, memory, processing speed) in healthy older adults. To theoretically embed the discussion, we refer to the revised Scaffolding Theory of Aging and Cognition. We found 31 eligible articles, with sample sizes ranging from n = 25 to n = 731 (median n = 104), and participant age ranging from 19 to 103. Several of these studies report positive correlated changes for specific regions and specific cognitive abilities (e.g. between structures of the medial temporal lobe and episodic memory). However, the number of studies presenting converging evidence is small, and the large methodological variability between studies precludes general conclusions. Methodological and theoretical limitations are discussed. Clearly, more empirical evidence is needed to advance the field. Therefore, we provide guidance for future researchers by presenting ideas to stimulate theory and methods for development.

The question of whether working memory training leads to generalized improvements in untrained cognitive abilities is a longstanding and heatedly debated one. Previous research provides mostly ambiguous evidence regarding the presence or absence of transfer effects in older adults. Thus, to draw decisive conclusions regarding the effectiveness of working memory training interventions, methodologically sound studies with larger sample sizes are needed. In this study, we investigated whether or not a computer-based working memory training intervention induced near and far transfer in a large sample of 142 healthy older adults (65 to 80 years). Therefore, we randomly assigned participants to either the experimental group, which completed 25 sessions of adaptive, process-based working memory training, or to the active, adaptive visual search control group. Bayesian linear mixed-effects models were used to estimate performance improvements on the level of abilities, using multiple indicator tasks for near (working memory) and far transfer (fluid intelligence, shifting, and inhibition). Our data provided consistent evidence supporting the absence of near transfer to untrained working memory tasks and the absence of far transfer effects to all of the assessed abilities. Our results suggest that working memory training is not an effective way to improve general cognitive functioning in old age. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)