Reserve-related activities and MRI metrics in multiple sclerosis patients and healthy controls: an observational study

Schwartz et al. BMC Neurology (2016) 16:108 DOI 10.1186/s12883-016-0624-1 RESEARCH ARTICLE Open Access Reserve-related activities and MRI metrics in multiple sclerosis patients and healthy controls: an observational study Carolyn E. Schwartz1,2*, Michael G. Dwyer3,4, Ralph Benedict5, Bianca Weinstock-Guttman5, Niels P. Bergsland3,6,7, Jei Li1,8, Murali Ramanathan5,9 and Robert Zivadinov3,5,10 Abstract Background: To examine whether past and current reserve-related activities make the brain less susceptible to MS pathology (i.e., lesions or disease-related atrophy). Methods: This secondary analysis of a cohort study included 276 healthy controls (HC), and 65 clinically isolated syndrome (CIS), 352 relapsing-remitting MS (RR) and 109 secondary- progressive MS (SPMS) patients. Past reserverelated activities comprised educational and occupational attainment. Current reserve-related activities comprised strenuous and non-strenuous activities. MRI was performed on 3 T scanner. Regression and non-parametric analysis examined relationships between MRI metrics and reserve-related activities. Results: Multivariate models (HC as referent) revealed significant interactions in predicting strenuous reserve-related activities with chronic lesion burden (for CIS), brain- (for RR & SPMS), subcortical- (for CIS, RR, & SPMS) and amygdala(for RR) volumes. Maximal Lifetime Brain Growth was higher for RR patients who engaged in running before and after diagnosis, rather than only before or never. Residual Brain Volume was higher in RR patients who did weights-exercise before and after diagnosis, as compared to only before. Conclusions: Reserve-related activities are related to brain health cross-sectionally in all MS subgroups, and longitudinally in RR patients. Consistent with reserve theory, RR patients who maintained strenuous activities had higher Maximal Lifetime Brain Growth and Residual Brain Volume. The study’s limitations are discussed, including the potential for recall bias and design limitations that preclude causal inference. Background A growing body of research suggests that reserve is a key concept underlying resilience to neurological disease [1]. Conceptualized as a buffer between measurable disease pathology and actual level of function, reserve can be studied by investigating brain maintenance [2]. Maintenance theories emphasize neuro-protective mechanisms. Current conceptualizations of reserve posit that past enrichment activities and current stimulating leisure activities play an important role in helping an individual to build and maintain reserve [3]. These “reserve-related activities” in theory bring both history and current activities * Correspondence: 1 DeltaQuest Foundation, Inc, 31 Mitchell Road, Concord, MA 01742, USA 2 Departments of Medicine and Orthopaedic Surgery, Tufts University Medical School, Boston, MA, USA Full list of author information is available at the end of the article into focus. In recent work, these activities are operationalized in terms of past activities (e.g., educational and occupational attainment) and current activities that are considered stimulating [4–7]. Recent research has documented a protective effect of stimulating leisure activities [6] in a broad range of disability domains in multiple sclerosis (MS) [4], such as physical, creative, intellectual, spiritual, and cultural enrichment. While both past and current reserve-related activities had notable cross-sectional and longitudinal associations with health and well-being, the current activities trumped past activities in explaining variance in health outcomes [4, 8]. Reserve-related activities provide a fundamental resource to the individual [9], and are associated with better health habits, maintaining employment, and living independently [8]. Distinct from different aspects of insight into one’s condition [10], high © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Schwartz et al. BMC Neurology (2016) 16:108 reserve-related activity engagement is associated with underlying cognitive appraisal processes that focus on the positive and more controllable aspects of their condition [11]. Longitudinal data supported a significant buffering effect of reserve, such that high-reserve individuals showed slower disability progression over six years of semi-annual follow-up [4]. These findings support the idea that symptom burden worsens as damage to the brain accumulates, and when reserve is exhausted, the progressive stage of the disease begins [12]. To date, however, very little research has addressed how these reserve-related activities relate to MRI metrics of brain health. Sumowski and colleagues reported that the negative effect of brain atrophy on information processing efficiency was attenuated at higher levels of reserve operationalized as education, such that MS subjects with higher levels of education were able to better withstand MS neuropathology without suffering cognitive impairment [13]. Further, early life enriching leisure activities were found to be more protective against memory deficits than cognitive inefficiency [14]. A retrospective analysis of neuroimaging data suggested that recreational activities protect against brain atrophy’s detrimental influence on cognition [15]. All of these prior studies suffered from small samples sizes and limited operationalizations of reserve or reserverelated activities. We thus sought to use a large and rich data set to test the hypothesis that engaging in past or current reserve-related activities will make the brain less susceptible to MS pathology in the forms of lesions or disease-related atrophy. The study data set includes a large sample with MRI data, including a substantial reference group of healthy controls who provide important referent information for the multivariate analyses. It includes a novel measure estimating residual brain volume, and includes data on exercise that captured events and pattern changes before and after MS diagnosis. Building on an initial descriptive study of differences in reserve-related activities between healthy individuals and people with MS, the present work examines how these reserve-related activities relate to MRI metrics of Maximal Lifetime Brain Growth and Residual Brain Volume. Methods Sample This secondary analysis utilized data from an ongoing prospective study of cardiovascular, environmental and genetic risk factors (...truncated)